Fluoride in Drinking Water A Scientific Review of EPA's Standards (2006) / Chapter Skim
Currently Skimming:
8 Effects on the Endocrine System
8 Effects on the Endocrine System
Pages 224-267
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 224... ...
and the World Health Organization (WHO 2002) mentioned secondary hyperparathyroidism in connection with discussions of skeletal fluorosis, but neither report examined endocrine effects any further.
|
From page 225... ...
EFFECTS ON THE ENDOCRINE SYSTEM 22 fected by deranged thyroid function (Goodman 2003) , making it among the most prevalent of endocrine diseases (Larsen et al.
|
From page 226... ...
, several older studies found that fluoride concentrations in thyroid tissue generally exceed those in most other tissue except kidney (e.g., Chang et al.
|
From page 227... ...
At 100 days, the high-fluoride groups had elevated serum T4 at all concentrations of iodine intake and elevated T3 in iodine-deficient animals. High fluoride intake significantly inhibited the radioiodine uptake in the low- and normal-iodine groups.
|
From page 228... ...
looked only for clinical evidence of goiter in domestic animals (cattle and buffaloes) showing signs of enamel or skeletal fluorosis; no hormone parameters (e.g., T4, T3, TSH)
|
From page 229... ...
Gedalia and Brand (1963) found an association between endemic goiter in Israeli girls and iodine concentrations in water but found no association with fluoride concentrations (<0.1-0.9 mg/L)
|
From page 230... ...
FIGURE 8-2 Goiter prevalence versus drinking water fluoride concentrations in six South African towns with adequate iodine concentrations. One town had a significantly lower prevalence of undernutrition than the other five Figure 8-2 towns and is not included in the line fitting.
|
From page 231... ...
and high (3-3.5 mg/L) fluoride concentrations in the drinking water.
|
From page 232... ...
The authors concluded that fluoride in excess may be inducing diseases that have usually been attributed to iodine deficiency and that iodine supplementation may not be adequate when excess fluoride is being consumed. Thyroid hormone disturbances were also noted in the control children, and urine and fluoride concentrations in the control children reflect higher fluoride intake than can be accounted for by the drinking water alone (Susheela et al.
|
From page 233... ...
In an earlier clinical study to examine the reported effects of fluoride on individuals with hyperthyroidism, Galletti and Joyet (1958) found that, in 6 of 15 patients, both basal metabolic rate and protein-bound iodine fell to normal concentrations, and the symptoms of hyperthyroidism were relieved after fluoride treatment.
|
From page 234... ...
. Uncertainty about total fluoride exposures based on water fluoride concentrations, variability in exposures within population groups, and variability in response among individuals generally have not been addressed.
|
From page 235... ...
EFFECTS ON THE ENDOCRINE SYSTEM 23 exactly what effects on thyroid function are likely at what concentration of fluoride exposure and under what circumstances. Suggested mechanisms of action for the results reported to date include decreased production of thyroid hormone, effects on thyroid hormone transport in blood, and effects on peripheral conversion of T4 to T3 or on normal deiodination processes, but details remain uncertain.
|
From page 236... ...
The possibility that either dental fluorosis (Chapter 4) or the delayed tooth eruption noted with high fluoride intake (Chapter 4; see also Short 1944)
|
From page 237... ...
Vitamin D deficiency was not found. In a review of skeletal fluorosis, Krishnamachari (1986)
|
From page 238... ...
of fluoride action with respect to effects on calcitonin and PTH secretion, but currently the significance of the elevated calcitonin concentrations associated with skeletal fluorosis is not clear.5 Parathyroid glands In humans, four small parathyroid glands are normally situated on the posterior surface of the thyroid. These glands produce PTH, a simple 84peptide hormone, which is the principal regulator of extracellular calcium (Bringhurst et al.
|
From page 239... ...
. In Vitro Studies Fluoride ion has been shown to be a potent inhibitor of PTH secretion in bovine and human parathyroid cells in vitro (Chen et al.
|
From page 240... ...
Control animals were fed drinking water containing fluoride at <0.5 mg/L. At 35 weeks, average serum immunoreactive PTH was reduced, but not significantly, in the fluoride-treated rats.
|
From page 241... ...
EFFECTS ON THE ENDOCRINE SYSTEM 241 (although some morphological changes occurred) , suggesting that normal parathyroid function was inhibited.
|
From page 242... ...
(1988, 1990) reported increased concentrations of biologically active PTH in osteoporosis patients receiving both calcium and sodium fluoride during short- and long-term treatments.
|
From page 243... ...
(1995) described a population study in China that examined adults in regions with various fluoride concentrations in the drinking water and either "normal" or "inadequate" nutrition in terms of protein and calcium intake; people in the sample were "healthy" rather than randomly selected.
|
From page 244... ...
(1997) examined adult volunteers in the United States who had lived at least 30 years in communities with natural fluoride concentrations in drinking water of 0.2, 1.0, or 4.0 mg/L.
|
From page 245... ...
versus fluoride intake for nine skeletal fluorosis patients (two of whom had moved to a low-fluoride area) and five controls (data from Teotia et al.
|
From page 246... ...
(1989) described a study of 260 children between 6 and 16 years old in an area of South Africa with endemic skeletal fluorosis (water fluoride concentrations of 8-12 mg/L)
|
From page 247... ...
The serum PTH in all groups was correlated with the fluoride intake (Figure 8-5) and with the severity of clinical and skeletal fluorosis.
|
From page 248... ...
There is renal conservation of calcium in spite of hyperparathyroidism, with no significant changes in serum biochemistry; urinary hydroxyproline excretion is significantly increased. In these conditions, an osteoporotic type of skeletal fluorosis occurs at a younger age, and growing children develop deformities due to bone softening.
|
From page 249... ...
For comparable fluoride intake, metabolic bone disease occurs in 90% of children with calcium deficiency versus 25% of children with adequate calcium intake. The authors concluded that the toxic effects of fluoride occur at a lower fluoride intake (>2.5 mg/day)
|
From page 250... ...
(1997) also found no significant effect of fluoride on blood calcium concentrations in people who lived in communities with different fluoride concentrations but presumably had adequate nutrition; PTH concentrations were not measured.
|
From page 251... ...
EFFECTS ON THE ENDOCRINE SYSTEM 21 the parathyroid or the thyroid parafollicular cells leads to a compensatory response from the other, but this has not been examined. Several studies have reported different responses among individuals or variability in group responses (Teotia and Teotia 1973; Teotia et al.
|
From page 252... ...
22 FLUORIDE IN DRINKING WATER Pineal gland The pineal gland is a small organ (150 mg in humans) located near the center of the brain.
|
From page 253... ...
, with the fluoride concentrations being positively related to the calcium concentrations in the pineal gland, but not to the bone fluoride, suggesting that pineal fluoride is not necessarily a function of cumulative fluoride exposure of the individual (Luke 1997, 2001)
|
From page 254... ...
. Potassium fluoride (7-10 mM, or fluoride at 133-190 mg/L)
|
From page 255... ...
1983) reported no difference in the menarcheal age of girls in a town with "optimal" fluoride concentration (1.09 mg/L in Kunszentmárton, median menarcheal age 12.779 years)
|
From page 256... ...
Statistically significant differences with respect to fluoride intake (as opposed to differences between normal and diabetic animals) were observed only for diabetic rats with fluoride at 50 mg/L.
|
From page 257... ...
In both types of diabetic rats, fluoride intake was very high because of the several-fold increase in water consumption, and corresponding plasma, soft tissue, and bone fluoride concentrations were elevated accordingly. Thus, any health effects related to plasma or bone fluoride
|
From page 258... ...
. In chronic exposures, effects on glucose metabolism occurred when plasma fluoride concentrations exceeded 0.1 mg/L (5 µmol/L)
|
From page 259... ...
(1993) reported impaired glucose tolerance in 40% of young adults with endemic fluorosis, with fasting serum glucose concentrations related to serum fluoride concentrations; the impaired glucose tolerance was reversed after 6 months of drinking water with "acceptable" fluoride concentrations (<1 mg/L)
|
From page 260... ...
These effects are summarized in Tables 8-1 and 8-2, together with the approximate intakes or physiological fluoride concentrations that have been typically associated with them thus far. Table 8-2 shows that several of the effects are associated with average or typical fluoride intakes of 0.05-0.1 mg/kg/day (0.03 with iodine deficiency)
|
From page 261... ...
dPlasma. are seen in humans at much lower fluoride intakes (or lower water fluoride concentrations)
|
From page 262... ...
In animals, effects on thyroid function have been reported at fluoride doses of 3-6 mg/kg/day (some effects at
|
From page 263... ...
; these exposures corresponded to plasma fluoride concentrations of 0.11-0.26 mg/L. Results attributed to altered calcitonin activity have also been found in experimental animals at a fluoride exposure of 2 mg/kg/day (Table 8-1)
|
From page 264... ...
. Impaired glucose tolerance in humans has been reported in separate studies at fluoride intakes of 0.07-0.4 mg/kg/day, corresponding to serum fluoride concentrations above about 0.1 mg/L.
|
From page 265... ...
Variability in response to fluoride exposures could be due to differences in genetic background, age, sex, nutrient intake (e.g., calcium, iodine, selenium) , general dietary status, or other factors.
|
From page 266... ...
, associated with increased likelihood of effects of fluoride exposures in individuals -- consideration of the impact of multiple contaminants (e.g., fluoride and perchlorate) that affect the same endocrine system or mechanism -- examination of effects at several time points in the same individuals to identify any transient, reversible, or adaptive responses to fluoride exposure.
|
From page 267... ...
, to reduce some of the uncertainty associated with comparisons of separate studies -- addressing uncertainties associated with exposure and response, including uncertainties in measurements of fluoride concentrations in bodily fluids and tissues and uncertainties in responses (e.g., hormone concentrations) -- reporting data in terms of individual correlations between intake and effect, differences in subgroups, and differences in percentages of individuals showing an effect and not just differences in group or population means.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.