http://www.nap.edu/openbook.php?record_id=2204
Health Effects of Ingested Fluoride
– 1993
Subcommittee on Health Effects of Ingested Fluoride
Committee on Toxicology
Board on Environmental Sutdies and Toxicology commission on Life
Sciences
National Research Council
•
Executive Summary:
Fluoridation of
drinking water has been a subject of controversy for decades. Over the
past 50 years, the incidence of dental caries (cavities) has declined
considerably in the United States, an important health advance that most
scientists attribute principally to increased access to fluoridated
water and dental products. According to the U.S. Centers for Disease
Control and Prevention, approximately 132 million Americans now receive
drinking water that contains fluoride, either naturally occurring or
added, at concentrations of 0.7 milligrams per liter (mg/L) or higher.
This report deals with
the possible toxic effects of ingested fluoride in humans. It does not
attempt to weigh fluoride's well-documented health benefits against its
possible adverse health effects.
|
http://www.nap.edu/catalog.php?record_id=11571
Fluoride in Drinking Water – 2006
A Scientific Review of EPA's Standards
Committee on Fluoride
in Drinking Water
National Research
Council
•
Executive Summary:
Fluoride is one of the drinking-water contaminants regulated by EPA. In
1986, EPA established an MCLG and MCL for fluoride at a concentration of
4 milligrams per liter (mg/L) and an SMCL of 2 mg/L. These guidelines
are restrictions on the total amount of fluoride allowed in drinking
water. Because fluoride is well known for its use in the prevention of
dental caries, it is important to make the distinction here that EPA’s
drinking-water guidelines are not recommendations about adding fluoride
to drinking water to protect the public from dental caries. Guidelines
for that purpose (0.7 to 1.2 mg/L) were established by the U.S. Public
Health Service more than 40 years ago. Instead, EPA’s guidelines are
maximum allowable concentrations in drinking water intended to prevent
toxic or other adverse effects that could result from exposure to
fluoride.
Because new research on fluoride is now available and because the Safe
Drinking Water Act requires periodic reassessment of regulations for
drinking-water contaminants, EPA requested that the NRC again evaluate
the adequacy of its MCLG and SMCL for fluoride to protect public health. |
• Dental fluorosis
In
general, the evidence supports the conclusion that fluoridation at the
recommended concentrations, in the absence of fluoride from other
sources, results in a prevalence of mild-to-very-mild (cosmetic) dental
fluorosis in about 10% of the population and almost no cases of moderate
or severe dental fluorosis. At 5 or more times the recommended
concentration, the proportion of moderate-to-severe dental fluorosis is
substantially higher. |
• Dental fluorosis
Since 1993, there have been no new studies of enamel fluorosis in U.S.
communities with fluoride at 2 mg/L in drinking water. Earlier studies
indicated that the prevalence of moderate enamel fluorosis at that
concentration could be as high as 15%. |
• Skeletal Fluorosis
Not addressed in the
1993 review |
• Skeletal Fluorosis
Skeletal fluorosis is a
bone and joint condition associated with prolonged exposure to high
concentrations of fluoride. Few clinical cases of skeletal fluorosis in
healthy U.S. populations have been reported in recent decades, and the
committee did not find any recent studies to evaluate the prevalence of
the condition in populations exposed to fluoride at the MCLG. …more
research is needed to clarify the relationship between fluoride
ingestion, fluoride concentrations in bone, and stage of skeletal
fluorosis before any conclusions can be drawn. |
• Bone strength and
the risk of bone fracture
In view of the
conflicting results and limitations of the current data base on fluoride
and the risk of hip or other fractures, the subcommittee concludes that
there is no basis at this time to recommend that EPA lower the current
standard for fluoride in drinking water for this end point. However, the
subcommittee recommends additional research to improve the current data
base. |
• Bone fractures
Overall, there was consensus among the committee that there is
scientific evidence that under certain conditions fluoride can weaken
bone and increase the risk of fractures. The majority of the committee
concluded that lifetime exposure to fluoride at drinking-water
concentrations of 4 mg/L or higher is likely to increase fracture rates
in the population, compared with exposure to 1 mg/L, particularly in
some demographic subgroups that are prone to accumulate fluoride into
their bones (e.g., people with renal disease). There were few studies
to assess fracture risk in populations exposed to fluoride at 2 mg/L in
drinking water. The best available study, from Finland, suggested an
increased rate of hip fracture in populations exposed to fluoride at
concentrations above 1.5 mg/L. However, this study alone is not
sufficient to judge fracture risk for people exposed to fluoride at 2
mg/L. Thus, no conclusions could be drawn about fracture risk or safety
at 2 mg/L. |
• Reproductive
effects in animals
The subcommittee
concludes that the fluoride concentrations associated with adverse
reproductive effects in animals are far higher than those to which human
populations are exposed. Consequently, ingestion of fluoride at current
concentrations should have no adverse effects on human reproduction. |
•
Reproductive and Developmental Effects
A
large number of reproductive and developmental studies in animals have
been conducted and published since the 1993 NRC report, and the overall
quality of that database has improved significantly. Those studies
indicated that adverse reproductive and developmental outcomes occur
only at very high contractions that are unlikely to be encountered by
U.S. populations. A few human studies suggested that high concentrations
of fluoride exposure might be associated with alterations in
reproductive hormones, effects on fertility, and developmental outcomes,
but design limitations make those studies insufficient for risk
evaluation. |
• Neurotoxicity and
Neurobehavioral Effects
Not addressed in the
1993 review |
•
Neurotoxicity and Neurobehavioral Effects
A
few epidemiologic studies of Chinese populations have reported IQ
deficits in children exposed to fluoride at 2.5 to 4 mg/L in drinking
water. Although the studies lacked sufficient detail for the committee
to fully assess their quality and relevance to U.S. populations, the
consistency of the results appears significant enough to warrant
additional research on the effects of fluoride on intelligence. More
research is needed to clarify the effect of fluoride on brain chemistry
and function. |
• Endocrine Effects
Not addressed in the
1993 review |
• Endocrine Effects
The chief endocrine
effects of fluoride exposures in experimental animals and in humans
include decreased thyroid function, increased calcitonin activity,
increased parathyroid hormone activity, secondary hyperparathyroidism,
impaired glucose tolerance, and possible effects on timing of sexual
maturity. Some of these effects are associated with fluoride intake that
is achievable at fluoride concentrations in drinking water of 4 mg/L or
less, especially for young children or for individuals with high water
intake. Many of the effects could be considered subclinical effects,
meaning that they are not adverse health effects. However, recent work
on borderline hormonal imbalances and endocrine-disrupting chemicals
indicated that adverse health effects, or increased risks for developing
adverse effects, might be associated with seemingly mild imbalances or
perturbations in hormone concentrations. Further research is needed to
explore these possibilities. |
• Effects on the
gastrointestinal system
The subcommittee
concludes that the available data show that the
concentrations of
fluoride found in drinking water in the United States are not likely to
produce adverse effects in the gastrointestinal system |
•
Effects on Other Organ Systems
The committee also considered effects on the gastrointestinal system,
kidneys, liver, and immune system.
There were no human studies on drinking water containing fluoride at 4
mg/L in which gastrointestinal, renal, hepatic, or immune effects were
carefully documented. Case reports and in vitro and animal studies
indicated that exposure to fluoride at concentrations greater than 4
mg/L can be irritating to the gastrointestinal system, affect renal
tissues and function, and alter hepatic and immunologic parameters. Such
effects are unlikely to be a risk for the average individual exposed to
fluoride at 4 mg/L in drinking water. However, a potentially susceptible
subpopulation comprises individuals with renal impairments who retain
more fluoride than healthy people do. |
.• Effects on the
renal systems
However, human
epidemiological studies have found no increase in renal disease in
populations with long-term exposure to fluoride at concentrations of up
to 8 mg/L of drinking water. The subcommittee concludes that available
evidence shows that the threshold dose of fluoride in drinking water for
renal toxicity in animals is approximately 50 mg/L. The subcommittee
therefore believes that ingestion of fluoride at currently recommended
concentrations is not likely to produce kidney toxicity in humans. |
• Effects on the
immune systems
Reports of hypersensitivity reactions in humans resulting from exposure
to sodium fluoride are mostly anecdotal. The weight of evidence shows
that fluoride is unlikely to produce hypersensitivity and other
immunological effects. |
• Genotoxicity
The subcommittee
concludes that the genotoxicity of fluoride should not be of concern at
the concentrations found in the plasma of most people in the United
States. |
• Genotoxicity
Many assays have been performed to assess the genotoxicity of fluoride.
Since the 1993 NRC review, the most significant additions to the
database are in vivo assays in human populations and, to a lesser
extent, in vitro assays with human cell lines and in vivo experiments
with rodents. The results of the in vivo human studies are mixed. The
results of in vitro tests are also conflicting and do not contribute
significantly to the interpretation of the existing database. Evidence
on the cytogenetic effects of fluoride at environmental concentrations
is contradictory. |
•
Carcinogenicity in animals and humans
The subcommittee
concludes that the available laboratory data are insufficient to
demonstrate a carcinogenic effect of fluoride in animals. The
subcommittee also concludes that the weight of the evidence from the
epidemiological studies completed to date does not support the
hypothesis of an association between fluoride exposure and increased
cancer risk in humans. Nonetheless, the subcommittee recommends
conducting one or more carefully designed analytical epidemiological
(case-control or cohort) studies to more fully evaluate the relation
between fluoride exposure and cancer,
|
•
Genotoxicity and Carcinogenicity
A
relatively large hospital-based case-control study of osteosarcoma and
fluoride exposure is under way at the Harvard School of Dental Medicine
and is expected to be published in 2006. That study will be an important
addition to the fluoride database, because it will have exposure
information on residence histories, water consumption, and assays of
bone and toenails. The results of that study should help to identify
what future research will be most useful in elucidating fluoride’s
carcinogenic potential. |
• Conclusions
Based on its review of available data on the toxicity of fluoride, the
subcommittee concludes that EPA's current MCL of 4 mg/L for fluoride in
drinking water is appropriate as an interim standard. At that level, a
small percentage of the U.S. population will exhibit moderate or even
severe dental fluorosis. However, the question of whether to consider
dental fluorosis a cosmetic effect or an adverse health effect and the
balancing of the health risks and health benefits of fluoride are
matters to be determined by regulatory agencies and are beyond the
charge or expertise of this subcommittee. The subcommittee found
inconsistencies in the fluoride toxicity data base and gaps in
knowledge. Accordingly, it recommends further research in the areas of
fluoride intake, dental fluorosis, bone strength and fractures, and
carcinogenicity. The subcommittee further recommends that EPA's interim
standard of 4 mg/L should be reviewed when results of new research
become available and, if necessary, revised accordingly. |
• Conclusions
The committee’s conclusions regarding the potential for adverse effects
from fluoride at 2 to 4 mg/L in drinking water do not address the lower
exposures commonly experienced by most U.S. citizens. Fluoridation is
widely practiced in the United States to protect against the development
of dental caries; fluoride is added to public water supplies at 0.7 to
1.2 mg/L. The charge to the committee did not include an examination of
the benefits and risks that might occur at these lower concentrations of
fluoride in drinking water. |