Fluoride

4. Can fluorides affect health?

• 4.1 Does fluoride affect bones in test animals?
• 4.2 Does fluoride cause cancer in test animals?
• 4.3 Does fluoride cause genetic mutations in cells or test animals?
• 4.4 Does fluoride affect reproduction or development in test animals?

4.1 Does fluoride affect bones in test animals?

The source document for this Digest states:

Effects on the skeleton, such as inhibition of bone mineralization and formation, delayed fracture healing and reductions in bone volume and collagen synthesis, have been observed in a variety of studies in which rats received fluoride orally for periods of 3–5 weeks. In medium-term exposure studies, altered bone remodelling, hepatic megalocytosis, nephrosis, mineralization of the myocardium, necrosis and/or degeneration of the seminiferous tubules in the testis were observed in mice administered fluoride in drinking-water (>4.5 mg/kg body weight per day) over a period of 6 months

Source & ©: IPCS "Environmental Health Criteria for Fluorides", (EHC 227), 
Summary of the Report, Chapter 1.6: Effects on laboratory mammals and in vitro test systems 

For more information, see the full IPCS document,
Chapter 7: Effects on laboratory mammals and in vitro test systems 

4.2 Does fluoride cause cancer in test animals?

The source document for this Digest states:

In a comprehensive carcinogenicity bioassay in which groups of male and female F344/N rats and B6C3F 1 mice were administered drinking-water containing up to 79 mg fluoride/litre as sodium fluoride for a period of 2 years, there was no statistically significant increase in the incidence of any tumour in any single exposed group. There was a statistically significant trend of an increased incidence of osteosarcomas in male rats with increasing exposure to fluoride. However, the incidence was within the range of historical controls.

Another 2-year carcinogenicity bioassay involving Sprague-Dawley rats exposed to up to 11.3 mg/kg body weight per day in the diet also found no statistically significant increase in the incidence of osteosarcoma or other tumours. Another study, which reported an increased incidence of osteomas in mice receiving up to 11.3 mg/kg body weight per day, is difficult to interpret, because the animals were infected with Type C retrovirus

Source & ©: IPCS "Environmental Health Criteria for Fluorides", (EHC 227), 
Summary of the Report, Chapter 1.6: Effects on laboratory mammals and in vitro test systems 

For more information, see the full IPCS document,
Chapter 7: Effects on laboratory mammals and in vitro test systems 

4.3 Does fluoride cause genetic mutations in cells or test animals?

The source document for this Digest states:

In general, fluoride is not mutagenic in prokaryotic cells. Although fluoride has been shown to increase the frequency of mutations at specific loci in cultured mouse lymphoma and human lymphoblastoid cells, these mutations are likely due to chromosomal damage rather than point mutations. Fluoride has been shown to be clastogenic in a variety of cell types. The mechanism of clastogenicity has been attributed to the effect of fluoride upon the synthesis of proteins involved in DNA synthesis and/or repair, rather than direct interaction between fluoride and DNA. In most studies in which fluoride was administered orally to rodents, there was no effect upon sperm morphology or the frequency of chromosomal aberrations, micronuclei, sister chromatid exchange or DNA strand breaks. However, cytogenetic damage in bone marrow or alterations in sperm cell morphology were reported when the substance was administered to rodents by intraperitoneal injection.

Source & ©: IPCS "Environmental Health Criteria for Fluorides", (EHC 227), 
Summary of the Report, Chapter 1.6: Effects on laboratory mammals and in vitro test systems 

For more information, see the full IPCS document,
Chapter 7: Effects on laboratory mammals and in vitro test systems 

4.4 Does fluoride affect reproduction or development in test animals?

The source document for this Digest states:

Reproductive or developmental effects were not observed in recent studies in which laboratory animals were administered fluoride in drinking-water. However, histopathological changes in reproductive organs have been reported in male rabbits administered (orally) 4.5 mg fluoride/kg body weight per day for 18–29 months, in male mice administered (orally) >4.5 mg fluoride/kg body weight per day for 30 days and in female rabbits injected subcutaneously with >10 mg fluoride/kg body weight per day for 100 days. Adverse effects on reproductive function have been reported in female mice administered (orally) >5.2 mg fluoride/kg body weight per day on days 6–15 after mating and in male rabbits administered (orally) >9.1 mg fluoride/kg body weight per day for 30 days.

Source & ©: IPCS "Environmental Health Criteria for Fluorides", (EHC 227), 
Summary of the Report, Chapter 1.6: Effects on laboratory mammals and in vitro test systems 

For more information, see the full IPCS document,
Chapter 7: Effects on laboratory mammals and in vitro test systems 
(see Chapter 7.8: Interaction with other subs  for the study pointing to neurotoxic effetcs by Mullenix et al.)