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EC number: 231-954-8 | CAS number: 7782-41-4
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: NTP study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Technical Report on the Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3F, Mice.
- Author:
- NTP
- Year:
- 1 990
- Bibliographic source:
- U.S Department of Health and Human Services. NTP TR 393, NIH Publication No. 91-2848, December 1990
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: NTP protocol
- Principles of method if other than guideline:
- 6-month repeated dose study.
- 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:
- No further details
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Progeny of C57BL/N6 female and C3H/HeN male mice, obtained from Charles River Laboratories, Wilmington, DE, were used in this study. Mice were 4 to 6 weeks old when placed on study. Their diet consisted of a semisynthetic low fluoride diet. The mice were kept in groups of ten in cages set at a temperture of 22-24 degC and of relative humidity 40-60%. The fluorescent light was 12 hours per day.
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on oral exposure:
- Groups of 8-12 mice of each sex received 0, 10, 30, 100, 200, 300 or 600 ppm sodium fluoride in deionised water ad libitum for 6 months.
- Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- The concentrations are nominal concentrations.
- Duration of treatment / exposure:
- 0, 10, 30, 100, 200, 300 or 600 ppm sodium fluoride in deionised water
- Frequency of treatment:
- Continous (ad libitum, in drinking water)
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 10, 30, 100, 200, 300 or 600 ppm
Basis:
nominal in water
- No. of animals per sex per dose:
- The method stated ten mice of each sex per dose group. However, some of the test animals were incorrectly sexed, resullting in 8-12 mice per sex per dose group.
- Control animals:
- other: One control group received de-ionised water and a low fluoride diet. One control group received sodium chloride and a low fluoride diet. An additional control group received standard diet.
- Details on study design:
- Groups of 8-12 mice of each sex received 0, 10, 30, 100, 200, 300 or 600 ppm sodium fluoride in deionised water ad libitum for 6 months. All test animals receiving water supplemented with sodium fluroide were provided with a low fluoride (<2.1 ppm) semisynthetic diet throughout the study. Three control groups were included in the studies of male and female mice; one received deionised drinking water and a low fluoride, semisynthetic diet, the second received sodium chloride supplemented deionized drinking water and a low fluoride, semisynthetic diet and the third received deionized water and a standard NIH-07 diet. At termination of the studies, the fluoride concentrations in urine, blood and bone were determined from samples collected from all surviving mice. Necropsy was performed on all animals, with histopathology at 300 and 600 ppm.
- Positive control:
- Not relevant
Examinations
- Observations and examinations performed and frequency:
- Animals were observed twice daily for mortality and morbidity, weighed initially, once weekly and at termination. Clinical observations recorded daily. Food consumption recorded every other week for the first 13 weeks and for 1 week during each of the last 3 months. Water consumption was recorded daily.
- Sacrifice and pathology:
- Necropsy was performed on all animals, with histopathological investigation of animals at 300 and 600 ppm.
- Other examinations:
- Fluoride concentrations in bone, blood and urine measured prior to necropsy
- Statistics:
- Not reported.
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):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Deaths occurred at 600 ppm (4 males, 9 females) and at 300 ppm (1 male). Signs of toxiicity (weakness, thin appearance, hunched posture) were seen at 600 ppm. Mice at 100, 200m 300 and 600 ppm had chalky white teeth; the lower incisors were more affected and were also chipped at higher dose levels.
BODY WEIGHT AND WEIGHT GAIN
Reduced weight gain was seen at 200, 300 and 600 ppm; food consumption was reduced in males at 600 ppm. Water consumption was unaffected by treatment.
GROSS PATHOLOGY
None
HISTOPATHOLOGY
Treatment-related findings were noted in the kidney, liver, testes and myocardium of decedents. Acute nephrosis was characterised by extensive multifocal degeneration and tubular necrosis and was diagnosed as the cause of death in these animals. Multifocal myocardial degeneration was also seen in two 600 ppm females. Liver changes consisted of scattered heptocellular hypertrophy and megalocytosis. The effects on the testes (degeneration/necrosis of the seminiferous tunules) were not considered to be directly related to treatment, but occur frequently in moribund mice. Effects were also noted on teh femur and (to a lesser extent) the tibia of mice at 50 ppm and greater. Changes are considered to be indicative of altered rates of bone deposition and remodelling. Effects on the teeth were seen at 300 and 600 ppm.
OTHER FINDINGS
The fluoride content of plasma, bone and urine increased with dose level.
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- < 50 ppm
- Sex:
- male
- Basis for effect level:
- other: Effects on bone
- Dose descriptor:
- LOEL
- Effect level:
- 50 ppm
- Sex:
- male
- Basis for effect level:
- other: Effects on bone
- Dose descriptor:
- NOEL
- Effect level:
- 50 ppm
- Sex:
- female
- Basis for effect level:
- other: Effects on bone
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Dose (ppm) |
Survival |
Mean Body Weight |
Final Weight relative to control (%) |
||
Initial |
Final |
Change |
|||
Male |
|||||
Controla |
9/9 |
16.9±0.4 |
40.2±1.0 |
23.3±1.1 |
100 |
Controlb |
10/10 |
18.6±0.4* |
41.6±0.6 |
23.0±0.7 |
103 |
Controlc |
11/11 |
17.8±0.4 |
39.2±1.0 |
21.4±1.0 |
97 |
10 |
9/9 |
17.3±0.5 |
43.1±1.5 |
25.8±1.8 |
107 |
50 |
10/10 |
18.0±0.6 |
41.1±1.1 |
23.1±1.3 |
102 |
100 |
10/10 |
19.2±0.8 |
41.5±1.1 |
22.3±1.3 |
103 |
200 |
10/10 |
17.9±0.7 |
36.5±1.2 |
18.6±1.4* |
91 |
300 |
7/8 |
18.8±0.7 |
38.1±1.1 |
19.0±1.4* |
95 |
600 |
5/9 |
17.4±0.4 |
32.0±1.6** |
14.8±1.9** |
80 |
Female |
|||||
Controla |
11/11 |
16.9±0.6 |
30.2±1.4 |
13.3±1.6 |
100 |
Controlb |
10/10 |
18.6±0.4 |
31.5±1.0 |
12.9±1.1 |
104 |
Controlc |
9/9 |
16.6±0.2 |
28.7±0.9 |
12.1±0.8 |
95 |
10 |
11/11 |
17.1±0.4 |
29.6±1.1 |
12.5±1.1 |
98 |
50 |
10/10 |
16.4±0.3 |
32.2±1.1 |
15.8±1.2 |
107 |
100 |
10/10 |
17.2±0.4 |
30.6±1.5 |
13.4±1.4 |
101 |
200 |
10/10 |
17.2±0.4 |
25.3±0.6** |
8.1±0.7* |
84 |
300 |
12/12 |
16.9±0.3 |
26.2±0.8* |
9.3±0.7* |
87 |
600 |
2/11 |
16.6±0.4 |
24.5±1.5 |
9.0±1.0 |
81 |
*Significantly different (P=0.05) from the control group by Dunn’s or Shirley’s test
**P<0.01
a Control group receiving semisynthetic, low fluoride diet and deionised water.
b Control group receiving semisynthetic, low fluoride diet and sodium chloride supplemented deionised water
c Control group receiving standard NIH-07 diet and deionised water.
Organs and Diagnoses |
300 ppm |
600 ppm |
Male Animals initially in study Early deaths
Kidney Nephrosis, multifocal
Liver Megalocytosis, multifocal Syncytial alteration, multifocal
Myocardium Mineralization, multifocal
Testis Necrosis Tubule, degeneration, multifocal Tubule, multinucleated giant cells, multifocal
Female
Animals initially in study Early deaths
Kidney Nephrosis, multifocal
Liver Megalocytosis, multifocal Syncytial alteration, multifocal
Myocardium Degeneration, multifocal Mineralization, multifocal |
8 1
1
1 1
1
1
1
12 0
0
0 0
0 0 |
9 4
2
4 4
4
3 2 1
11 9
2
7 7
2 4 |
Applicant's summary and conclusion
- Conclusions:
- Skeletal effects of fluoride were seen at all dose levels in this study.
- Executive summary:
In the 6 month studies in mice, 4/9 males and 9/11 females receiving 600 ppm sodium fluoride and 1/8 male given water containing 600 ppm died.
The fluoride content of urine and bone increased with the concentration of sodium fluoride in the drinking water in both sexes of mice. Bone fluoride concentration were as high as 14.8 µg/mg of ashed bone in male mice receiving 600 ppm sodium fluoride in water. The bone fluoride content found in mice was somewhat greater than that found in rats given comparable sodium fluoride content. This maybe due to a greater water intake on a body weight basis by mice than by rats resulting in higher exposures. Plasma fluoride concentrations in mice showed a good dose relationship and appeared increased in groups receiving water concentrations of 50 ppm of sodium fluoride or higher.
Histopathologic findings for mice are consistent with previously recognised toxic effects. The acute nephrosis observed in the kidneys was probably the most likely cause of death. Lesions were also observed on the incisor teeth, femur and tibia of mice
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