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Toxicological information

Repeated dose toxicity: oral

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Administrative data

repeated dose toxicity: oral
other: review of effects of chronic exposure of human population
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
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Expert committee review including assessment of fluoride toxicity.

Data source

Reference Type:
review article or handbook
Fluoride in Drinking Water: A Scientific Review of EPA's Standards
Committee on Fluoride in Drinking Water, National Research Council
Bibliographic source:
National Academies Press, Washington ISBN: 0-309-65796-2

Materials and methods

Principles of method if other than guideline:
Expert review of fluoride intake and effects on human health.

Test material

Details on test material:
Inorganic fluoride in drinking water.
Fluoride is a hydrolysis product of the reaction of LiPF6 with water.

Test animals

other: Humans

Administration / exposure

Details on oral exposure:
Intake in drinking water.

Results and discussion

Results of examinations

Details on results:
Total inorganic fluoride intake in the USA, from nonwater plus fluoridated drinking water sources, has been estimated to be up to 258 µg/kg/day in infants and up to 79 µg/kg/day in adults.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Identified human health effects of excess fluoride intake include fluorosis of the dental enamel: severe fluorosis affects about 10% of children in US communities drinking water containing fluoride at or close to 4 mg/l. Skeletal fluorosis and increased propensity to bone fracture may also be increased in populations drinking water with 4 mg fluoride/l, but the data on these endpoints was considered uncertain.

Applicant's summary and conclusion

Fluoride intake in drinking water at levels close to or above 4 mg/l is associated with dental fluorosis and perhaps also bone fluorosis and/or weakening.