indicate a human health risk. This included an evaluation of in vitro assays, animal research, and human studies (conducted in the United States and other countries). Positive and negative results were considered, as well as mechanistic and nonmechanistic information. The collective evidence was considered in perspective with exposures likely to occur from fluoride in drinking water at the MCLG or SMCL.

In evaluating the effects of fluoride, consideration is given to the exposure associated with the effects in terms of dose and time. Dose is a simple variable (such as mg/kg/day), and time is a complex variable because it involves not only the frequency and duration of exposure but also the persistence of the agent in the system (kinetics) and the effect produced by the agent (dynamics). Whether the key rate-limiting events responsible for the adverse effect are occurring in the kinetic or in the dynamic pathway is important in understanding the toxicity of a chemical and in directing future research (see Rozman and Doull 2000). The committee also attempts to characterize fluoride exposures from various sources to different subgroups within the general population and to identify subpopulations that might be particularly susceptible to the effects of fluoride.

The remainder of this report is organized into 10 chapters. Chapter 2 characterizes the general public’s exposure to fluoride from drinking water and other sources. Chapter 3 provides a description of the chemistry of fluoride and pharmacokinetic information that was considered in evaluating the toxicity data on fluoride. In Chapters 4-9, the committee evaluates the scientific literature on adverse effects of fluoride on teeth, the musculoskeletal system, reproduction and development, the nervous system, the endocrine system, the gastrointestinal system, the kidneys, the liver, and the immune system. Chapter 10 evaluates the genotoxic and carcinogenic potential of fluoride. Finally, Chapter 11 provides an assessment of the most significant health risks from fluoride in drinking water and its implications for the adequacy of EPA’s MCLG and SMCL for protecting the public.