Registration Dossier
Registration Dossier
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: 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

Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according to generally vaild procedures and accordinig to GLP guidelines. All parameters described are closely related or comparable to guideline methods.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Developmental toxicity evaluation of sodium fluoride administered to rats and rabbits in drinking water
- Author:
- Heindel, Jerrold J., Hudson K. Bates, Catherine J. Price, Melissa C Marr, Christina B Myers and Bernard A Schwetz
- Year:
- 1 996
- Bibliographic source:
- Fundamental and Applied Toxicology 30, 162-177
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Sodium fluoride
- EC Number:
- 231-667-8
- EC Name:
- Sodium fluoride
- Cas Number:
- 7681-49-4
- IUPAC Name:
- sodium fluoride
- Details on test material:
- - Name of test material (as cited in study report): sodium fluoride
- Analytical purity: >99%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, NC
- Weight at study initiation: mean body weights/group ranged from 248 to 253 g
- Fasting period before study: no
- Diet (e.g. ad libitum): ad libitium
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 (average)
- Humidity (%): 55% (average)
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- Animals were exposed to 0, 50, 150 or 300 ppm sodium fluoride in drinking water
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Preexposure analysis of drinking water solutions demontrated the concentrations of sodium fluoride to be within a range of 104-107% of target concentrations.
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:1
- Length of cohabitation: overnight
- Any other deviations from standard protocol: The morning on which sperm were found in a vaginal lavage was designated as GD 0. - Duration of treatment / exposure:
- Gestation days 6 through 15
- Frequency of treatment:
- ad libitum - drinking water
- Duration of test:
- Terminated on Gestation day 20
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 50, 150 or 300 ppm sodium fluoride
Basis:
nominal in water
- No. of animals per sex per dose:
- 26
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: The sodium fluoride concentrations tested were 50, 150 and 300 ppm which corresponded to approximately 7.5, 22.5, and 45 mg/kg/day based on an estimated water consumption of 150 mL/kg body weight/day. The LD50 for sodium fluoride in rats is at least 52 mg/kg/day or approximately 350 ppm if administered in drinking water. The concentrations were chosen after consideration of data from the NTP 14-day study in which female rats given 400 ppm sodium fluoride in drinking water showed decreasesd body weight and water consumption and clinical signs of toxicity (dehydration , lethargy, and hunched posture) while 800 ppm killed all the animals. The high dose (300 ppm) was chosen in an effort to induc e some maternal toxicity while avaoiding the potentially confounding effects of dehydration seen at the 400 ppm level in the 14-day study. The 300 ppm level was anticipated to be a nonlethal exposure based on the lack of lethality among rats exposed to 300 ppm sodium fluoride in the NTP 6-month drinking water studty and 50 ppm low level was expected to produce no maternal toxicity based on a lack of effects related to sodium fluoride consumption in the NTP 2-year toxicity study at exposures up to 100 ppm.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily beginning on gestation day 6
BODY WEIGHT: Yes
- Time schedule for examinations: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations:0, 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: liver, kidney and uterus
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [all per litter]
- Skeletal examinations: Yes: [all per litter]
- Head examinations: Yes: [half per litter] - Statistics:
- General linear model (GLM) procedures were applied for the analyses of varience (ANOVA) of maternal and fetal parameters. Prior to GLM-ANOVA analysis, an arcsine-square root transformation was performed on all litter-derived percentage data to normalize the means and Bartlett's test for homogeneity of variance was performed on all data to be analyzed by ANOVA. GLM-ANOVA anyalysis determined the significance of dose-response relationships and the significance of dose effects, replicate effects, and dose x replicate interactions. When ANOVA revealed a significant (p<0.05) dose effect, Dunnett's test and Williams' test were used to compare treated to control groups. One-tailed tests wre used for all pairwise comparisons except maternal body and organ weeights, food and water consuumption , fetal body weight, and percentage of males per litter. If a significant (p<0.05) dose x replicate interaction occurred, then the data for that endpoint were analyzed separately for dose effects witnin each replicate in the study, as well as for all replicates combined. Nominal scale measures were analyzed by a X2 test for independence and by a test for linear trend on proportions. When a X2 test showed significant experinent-wise differences, a one-tailed Fisher's exact test was used for pairwise comparisons of treatment and control groups.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
No animals died during the course of the study. No treatment-related clinical signs were observed in confirmed-pregnant animlsa during or after administration of sodium fluoride. Maternal body weight gain during the first 2 days of exposure (GD 6 to 8) was significantly reduced at 300 ppm relative to controls. Maternal water consumption of rats given 300 ppm sodium fluoride was significantly decreased for each period of observation from GD 6 to 15. Maternal food consumption was also decreased in the animals given 300 ppm sodium fluoride from GD 8 to 10, but did not differ from controls for any other period of measurement. Maternal liver and kidney weights on GD 20 were not differenct from control . Examination of uteri demonstrated that 100% (26/26), 96% (25/26), 89% (23/26), and 96% (25/26) of the mated animals in the control throught high-dose groups were pregnant.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- ca. 150 ppm
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEC
- Effect level:
- ca. 300 ppm
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEC
- Effect level:
- > 300 ppm
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No embryotoxic or teratogenic effects related to exposure to sodium fluoride in drinking water was observed at any dose concentration.
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Maternal exposure to sodium fluoride at conentrations up to 300 ppm (approximately 27 mg/kg/day) during organogenesis (gestation days 6 to 15) did not significantly affect the frequency of postimplantation loss, mean fetal body weight/litter, or external, visceral or skeletal malformations in the rat.
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.
