are few and have some significant shortcomings in design and power, limiting their impact.
A large number of reproductive and developmental studies in animals have been conducted and published since 1990, and the overall quality of the database has improved significantly. High-quality studies in laboratory animals over a range of fluoride concentrations (0-250 mg/L in drinking water) indicate that adverse reproductive and developmental outcomes occur only at very high concentrations. A few studies of human populations have suggested that fluoride might be associated with alterations in reproductive hormones, fertility, and Down’s syndrome, but their design limitations make them of little value for risk evaluation.
Studies in occupational settings are often useful in identifying target organs that might be susceptible to disruption and in need of further evaluation at the lower concentrations of exposure experienced by the general population. Therefore, carefully controlled studies of occupational exposure to fluoride and reproductive parameters are needed to further evaluate the possible association between fluoride and alterations in reproductive hormones reported by Ortiz-Perez et al. (2003).
Freni (1994) found an association between high fluoride concentrations (3 mg/L or more) in drinking water and decreased total fertility rate. The overall study approach used by Freni has merit and could yield valuable new information if more attention is given to controlling for reproductive variables at the individual and group levels. Because that study had design limitations, additional research is needed to substantiate whether an association exists.
A reanalysis of data on Down’s syndrome and fluoride by Takahashi (1998) suggested a possible association in children born to young mothers. A case-control study of the incidence of Down’s syndrome in young women and fluoride exposure would be useful for addressing that issue. However, it may be particularly difficult to study the incidence of Down’s syndrome today given increased fetal genetic testing and concerns with confidentiality.