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EC number: 244-334-7 | CAS number: 21324-40-3
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- two-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- other: Information on major hydrolysis product of the registered substance (released rapidly on contact with water/moisture).
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study report published in a peer-reviewed journal. Unlike some other available studies, considered reliable for NOAEL determination in the HF EU RAR.
- Justification for type of information:
- Part of weight-of-evidence approach adapting the information requirements of Annex VIII 8.7.1, Annex XI 8.7.3 and Annex X 8.7.3 under REACH in accordance with Annex XI Section 1.2. Lithium hexafluorophosphate is reactive and unstable in water and air. Reaction in contact with water proceeds rapidly, with release of hydrogen fluoride (forming hydrofluoric acid). Such local generation of hydrogen fluoride/hydrofluoric acid at the site of contact with skin or other membranes, with consequent potential for serious local tissue damage, is a major cause of the observed corrosivity of the substance, and secondary tissue necrosis due to localised free fluoride ion concentrations is also a likely contributor to this (Kirkpatrick Enion and Burns, 1995): delayed onset of deep tissue damage and pain is known after skin contact with HF solutions below 20% in concentration (US ATDSR, 2001). Ethical and practical reasons therefore make it inappropriate to consider reprotoxicity testing of lithium hexafluorophosphate in animals and since information is available on the reprotoxicity of the hydrolysis products hydrogen fluoride, lithium fluoride and phosphoric acid, this is also scientifically unnecessary (see separate read-across justification in Section 13). In accordance with Annex XI, 1.2 of the REACH Regulation testing is not scientifically necessary based on weight-of evidence approach. On humane grounds, as indicated in Article 15, 2 of Directive 2010/63/EU, animal testing for reprotoxicity (likely to involve severe pain, suffering or distress) should not be performed.
Data source
Reference
- Reference Type:
- publication
- Title:
- Multigenerational evaluation of sodium fluoride in rats
- Author:
- Collins T.F.X. et al
- Year:
- 2 001
- Bibliographic source:
- Food and Chemical Toxicology 39, 601-613
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- GLP compliance:
- yes
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:
- High purity (equal to USP reference sample).
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: CD-BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Bodyweight 51-75g at start of 1-week acclimatisation pre-study.
Fed on low-fluoride diet (F- 7.95 ppm)
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- other: water having <0.2 ppm F-
- Details on mating procedure:
- After 10 treatment weeks, mated 1:1 (if unmated, remated after 1 week).
Mating confirmation: sperm in vaginal lavage. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- F- by potentiometric titration.
- Duration of treatment / exposure:
- P generation: 10 weeks, then up to 3 mating weeks plus 21 postnatal days.
F1 generation: 10 weeks from postnatal day 21, then up to 3 mating weeks, plus 20 postnatal days.
F1 subset: dosing continued to postnatal day 90. - Frequency of treatment:
- Continuous
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 25, 100, 175, 250 ppm
Basis:
nominal in water
- No. of animals per sex per dose:
- 48M+48F/group
- Control animals:
- other: yes, <0.2 ppm in water
- Details on study design:
- P males: transferred to another (male fertility) study after mating.
P females: 8/48 terminated and examined at gestation day 20.
F1 pups: litter size controlled to 10 by postnatal day 4 cull.
F1 post-weaning: group sizes 36M+36F taken forward for mating, 10M+10F treated up to postnatal day 90. - Positive control:
- No
Examinations
- Parental animals: Observations and examinations:
- Daily observations for toxic reaction during treatment.
Food and water consumption monitored.
At termination (10 rats/sex/group: P, F1 weanlings, F1 adults):
- gross lesions and organ weights recorded
- full tissue list subjected to histopathology examination (controls and 250 ppm groups)
- less complete tissue list subjected to histopathology examination (other groups). - Litter observations:
- F1 pups: observations including sexing and weighing on postnatal days 0,4,7,14,21
- Postmortem examinations (parental animals):
- Gross abnormalities, organ weights.
- Postmortem examinations (offspring):
- Gross abnormalities, organ weights.
- Statistics:
- Fisher's exact, ANOVA, ANCOVA, LSD tests applied to appropriate parameters.
- Reproductive indices:
- Females:
Mating index (sperm-positive/placed for mating, %).
Fertility index 1 (littering/sperm-positive, %).
Fertility index 2 (littering/placed for mating, %).
Time to mating.
Males:
Mating index (giving sperm-positive females/placed for mating, %).
Fertility index 1 (producing litter/giving sperm positive females, %).
Fertility index 2 (producing litter/placed for mating, %). - Offspring viability indices:
- F1 progeny numbers recorded:
- implants
- total born and born alive
- alive on day 4 (pre-cull)
- post-cull survivors on days 4, 7, 14 and 21.
F1 bodyweights recorded:
- on days 0 and 4
- post-cull on days 4, 7, 14, and 21.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced food consumption and weight gain in P males at 250 ppm only.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced food consumption and weight gain in P males at 250 ppm only.
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Growth lines in teeth at 250 ppm. Occasional stomach ridge hyperkeratosis in a few P and F1 rats (considered a response to NaF).No other differences between test and control animals, in reproductive or other organs/tissues.
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Test substance intake: Calculated fluoride intakes: P males, 10.5 mgF-/kg/day; P females, 12.3 mgF-/kg/day. F1 males, 10.9 mgF-/kg/day; F1 females, 12.7 mgF-/kg/day.
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- Mating indices (>90%) unaffected by treatment. Male and female reproduction indices did not differ significantly between test groups and controls.
Details on results (P0)
Effect levels (P0)
- Dose descriptor:
- NOEL
- Remarks:
- for sodium fluoride in drinking water
- Effect level:
- 250 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on calculated intake, 250 ppm NaF was equivalent to 28.4 mg NaF/kg/day or 12.8 mgF-/kg/day. No adverse effects on reproduction. No effect on bodyweight-relative organ weights or brainweight-relative organ weights.
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- NOEL
- Remarks:
- Sodium fluoride in drinking water
- Generation:
- F1
- Effect level:
- 250 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on calculated intake, 250 ppm NaF was equivalent to 28.4 mg NaF/kg/day or 12.8 mgF-/kg/day. No adverse effects on reproduction. No effect on bodyweight-relative organ weights or brainweight-relative organ weights.
Results: F2 generation
Effect levels (F2)
- Dose descriptor:
- NOEL
- Remarks:
- Sodium fluoride in drinking water
- Generation:
- F2
- Effect level:
- 250 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on calculated intake, 250 ppm NaF was equivalent to 28.4 mg NaF/kg/day or 12.8 mgF-/kg/day. No adverse effects on reproduction. No effect on bodyweight-relative organ weights or brainweight-relative organ weights.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Administration of fluoride in drinking water, at levels up to a calculated intake of 12.8 mg F-/kg/day, had no adverse effect on reproduction and produced no significant systemic toxicity in rats.
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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