Latest Submission to NRC Panel on Fluoride/Bone
March 15, 2004
Issue #4: Latest Submission to NRC Panel on Fluoride/Bone
On Friday, March 12th, and Monday, March 15th, I submitted the following information to the US National Research Council (NRC). As many of you probably know, the NRC has been requested by the US Environmental Protection Agency (EPA) to review the adequacy of EPA’s current safe drinking water standard for fluoride (the Maximum Contaminant Level - MCL). See: http://www.fluoridealert.org/nrc-review.htm
In the following submission, I start by summarizing the data on fluoride & bone damage which I’ve previously sent the panel (see: http://www.fluoridealert.org/bone-data.pdf ; http://www.fluoridealert.org/nrc-letter.pdf ; http://www.fluoridealert.org/nrc-letter2.pdf ).
I then provide hard copies of, and commentary on, 11 significant studies on fluoride & bone. I have included my comments on these papers below.
Based on the following information, it is clear that the current MCL can not be relied on to protect against fluoride-induced bone damage, including: reduced bone strength, reduced bone density, increased mineralization defects, exacerbation of bone disease in people with kidney disease, and skeletal fluorosis of varying severity.
Thus, based on the issue of bone damage alone, the MCL needs to be lowered.
This fact has important implications for EPA’s recent decision (January 23, 2004) to allow DOW AgroScience the right to spray a new fluoride pesticide - sulfuryl fluoride - on a wide range of foodstuffs prepared in the US. See EPA’s ruling here.
EPA’s decision to give DOW the green light was entirely predicated on the adequacy of the current 4 ppm MCL. Hence, if the current NRC panel concludes that the 4 ppm MCL is inadequate than the EPA will have to revise its policy on sulfuryl fluoride.
The NRC’s review of EPA’s fluoride MCL is expected sometime next year (2005). In the meantime, the Fluoride Action Network is working on an appeal to the EPA’s sulfuryl fluoride ruling, which we hope to have completed by next weekend. (EPA’s deadline is March 23, 2004). I will send out more information about the content of our appeal shortly.
Michael Connett
Editor, FAN Science-Watch
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Summation of Data on Fluoride & Bone Damage (at Exposure Levels Relevant to Current MCL)
by Michael Connett
March 2004
1) Water fluoride content
EPA's current MCL of 4 ppm equals or exceeds:
- The concentrations (1.2-1.4 ppm) found to produce skeletal fluorosis in India and China. (SOURCE: Singh 1961; Jollly 1970; Siddiqui 1970; Xu 1997; Choubisa 2001; Bo 2003)
- The concentrations (1.7-2.0 ppm; 1.7-2.6 ppm; 2.4-3.5 ppm) found to produce skeletal fluorosis in the US. (SOURCE: Sauerbrunn 1965; Juncos 1972; Johnson 1979)
- The concentrations (1.5+ ppm) found to produce mineralization defects in bone. (SOURCE: Arnala 1985)
- The concentrations (4 ppm) found to reduce the density of human bone. (SOURCE: Phipps 1990; Sowers 1991)
- The concentrations found to produce moderate/severe dental fluorosis in over 30% of children drinking the water. (SOURCE: Dean 1942; NRC 1993).
-The concentrations (1-4 ppm) found to increase bone fracture rates. (SOURCE: Jacobsen 1990, 1992; Cooper 1991; Keller 1991; Sowers 1991; Danielson 1992; May and Wilson 1992; Jacqmin-Gadda 1995, 1998; Kurttio 1999; Hegmann 2000; Phipps 2000; Alarcon-Herrera 2001; and Li 2001)
2) Daily Fluoride Dose
The daily doses (8 mg/day from 2 liters of water consumption; 12 mg/day from 3 liters; 16 mg/day from 4 liters) produced at EPA's current MCL equal, exceed, or lack an adequate margin of safety for:
- The doses (2-8 mg) estimated to cause the early stages of skeletal fluorosis. (SOURCE: Singh & Jolly 1970)
- The doses (2.5+ mg) estimated to produce bone damage in children with calcium deficiency in India. (SOURCE: Teotia 1998)
- The dose (5 mg) which the NIPHEP in The Netherlands recommend as the maximum daily intake to protect against skeletal fluorosis. (SOURCE: NIPHEP 1989)
- The doses (9.4-12 mg) found to cause clinical skeletal fluorosis in India, Tibet, and China. (SOURCE: Teotia 1998; Cao 2003; Bo 2003)
- The doses (10+ mg) which the Institute of Medicine and the National Research Council estimate cause skeletal fluorosis. (SOURCE: NRC 1993; IOM 1997)
- The dose (14 mg for 70 kg adult) which Health Canada estimates will cause skeletal fluorosis. (SOURCE: Liteplo 1994)
- The dose (14 mg) which the World Health Organization estimates will have adverse effects on the skeleton. (SOURCE: WHO 2002)
- The doses (14-25 mg) which Roholm estimated to cause skelelal fluorosis. (SOURCE: Roholm 1937; Brun 1941)
- The doses (21-25 mg) found to cause bone fractures in short-term clinical trials. (SOURCE: Inkovaara 1975; Dambacher 1986; Hedlund 1989; Bayley 1990; Orcel 1990; Gutteridge 2002)
3) Serum fluoride content
The serum fluoride levels (up to 14.1 umol/l – SOURCE: Johnson 1979) produced at half (i.e. 2 ppm) the EPA's MCL equal or exceed:
- The serum fluoride levels (2-5 umol/L) associated with altered bone cell activity. (SOURCE: Farley 1983; Taves 1970; Pak 1989)
- The serum fluoride levels (5+ umol/L) which Mayo Clinic scientists estimate could cause bone damage. (SOURCE: Johnson 1979)
- The serum fluoride levels (5.3-14.6 umol/L) found in humans with skeletal fluorosis. (SOURCE: Singla 1976; Li 1986; Li 1990; Susheela 1996;. Barot 1998; Savas 2001; Yildiz 2003)
- The serum fluoride levels (7.6+ umol/L) associated with mineralization defects in rat bone. (SOURCE: Turner 1996; see also: Ittel 1992)
- The serum fluoride levels (8.2 umol/L) associated with increased osteosarcomas (bone cancers) in rats. (SOURCE: NTP 1990)
- The serum fluoride levels (9 - 10.8 umol/L) associated with reduced bone strength in rats. (SOURCE: Turner 1995; Turner 1996; Turner 2001).
- The serum fluoride levels (10.5-12.1 umol/L) associated with severe dental fluorosis in an area with severe endemic fluorosis. (SOURCE: Jin 2003).
4) Bone fluoride content
The *average* bone fluoride levels (6,100-6,400 ppm; SOURCE: Zipkin 1958; Gordin & Corbin 1992) found in adults at the EPA's MCL equal or exceed:
- The bone fluoride levels (2,500 - 4,500 ppm) associated with reduced strength of animal bone. (SOURCE: Mosekilde 1987; Turner 1993; Lafage 1995; Sogaard 1995)
- The bone fluoride levels (3,400 ppm) associated with increased mineralization defects in people with kidney disease. (SOURCE: Ng 2004)
- The bone fluoride levels (3,500-4,000 ppm) associated with bone changes in occupational skeletal fluorosis. (SOURCE: Franke 1975; Baud 1978)
- The bone fluoride levels (4,570 ppm) associated with bone mineralization defects in humans. (SOURCE: Boivin 1993)
- The bone fluoride levels (6,000 ppm) which the US Public Health Service associates with the first clinical phase of skeletal fluorosis. (SOURCE: PHS 1991)
- The bone fluoride levels (6,100 ppm) found in a US citizen with crippling skeletal fluorosis. (SOURCE: Sauerbrunn 1965)
- The bone fluoride levels (6,000-7,000 ppm) estimated to be the "toxic threshold" by modern proponents of fluoride as a drug for osteoporosis. (SOURCE: Zerwekh 1996)
References for Bone Data:
To see the references, click here
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Comments on Submitted Papers:
Paper # 1 :
Sowers M, et al. (1991). A prospective study of bone mineral content and fracture in communities with differential fluoride exposure. American Journal of Epidemiology 133: 649-660.
This study reports a higher rate of bone fracture, and an increased rate of bone loss, in a US community with 4 ppm fluoride in the water versus a community with 1 ppm. The study highlights the problematic nature of EPA’s assumption (when setting the fluoride MCL in 1985) that crippling skeletal fluorosis is the only relevant adverse bone effect which the MCL should protect against.
Common sense alone should indicate that if fluoride can cripple the human skeleton, it can probably cause subtler bone damage before it cripples. This study by Sowers suggests that bone fracture and reduced bone density are 2 such bone effects which can occur before the skeleton is crippled (e.g. before the spinal column is fused into one calcified immobile bone, and before extensive joint calcifications occur throughout the rest of the body).
Other bone effects which may occur before the skeleton is crippled, include:
1) Arthritic pains which mimic rheumatoid and osteoarthritis;
2) Mineralization defects in bone (see papers # 5 & 6 in this packet);
3) Exacerbation of bone disease in kidney patients (see papers # 6 & #7 in this packet);
4) Clinical bone changes which mimic ankylosing spondylitis, Diffuse Idiopathic Skeletal Hyperostosis (DISH), osteopetrosis, rickets, and Paget’s Disease.
Paper # 2:
Phipps KR, Burt BA. (1990). Water-borne fluoride and cortical bone mass: A comparison of two communities. Journal of Dental Research 69: 1256-1260.
Consistent with Sowers (1991), this study also reports an increased rate of bone loss in a US community with 3.5 ppm fluoride in its water versus a community with 0.7 ppm. As with Sowers (1991), this study highlights the problems with EPA’s focus on crippling skeletal fluorosis as the only adverse bone effect to protect
Paper # 3:
Johnson W, et al. (1979). Fluoridation and bone disease in renal patients. In: Johansen E, Taves DR, Olsen TO, Eds. Continuing Evaluation of the Use of Fluorides. AAAS Selected Symposium. Westview Press, Boulder, Colorado. pp. 275-293.
I believe this study is extremely important. Written by 2 scientists at the Mayo Clinic (William Johnson & Jennifer Jowsey), as well as Donald Taves from the University of Rochester, this study reports on the Mayo Clinic’s experience with fluoride-induced bone damage in people with kidney disease. As with Juncos & Donadio (1972), this study found that people with kidney disease developed what the authors believed to be fluoride-induced bone damage by drinking water with “just” 1.7 to 2 ppm. What makes this study particularly strong, is that, unlike the earlier study from Juncos & Donadio (1972), the authors here took fluoride measurements of the patients’ serum and bones, and found both to be greatly elevated. In addition, the authors found that when they switched the patient with the severest case of bone disease to a fluoride-free water supply, his symptoms (e.g. bone pain) subsided. In light of these and other findings, the authors conclude:
“The available evidence suggests that some patients with long-term renal failure are being affected by drinking water with as little as 2 ppm fluoride… The finding of adverse effects in patients drinking water with 2 ppm of fluoride suggests that a few similar cases may be found in patients imbibing 1 ppm, especially if large volumes are consumed, or in heavy tea drinkers and if fluoride is indeed a cause.”
Again, I believe that if the EPA’s MCL is to fulfill its mission to “protect the most vulnerable”, than it can not just focus on crippling skeletal fluorosis as the only adverse bone effect to protect against (as is currently the case). Rather, the MCL should seek to prevent the pre-crippling effects as well, which in this case is a fluoride-induced exacerbation of bone disease in kidney patients.
Interestingly, when the EPA established its MCL in 1985, it acknowledged that the current MCL could not be relied on to protect people with kidney disease. To quote:
"The Agency feels that this RMCL provides an adequate margin of safety except in those very extreme cases involving severely renally impaired individuals who consume unusually high levels of fluoride due in part to polydipsia and other confounding factors" (emphasis added; Federal Register, Nov 14, 1985, p. 47152).
“Except” is the key word here. It stands in clear contrast to the EPA’s emphasis of protecting the most vulnerable. To quote:
"[T]he Agency is acutely aware of sensitive subgroups in the population. Under the SDWA, EPA is charged with setting standards to protect the most sensitive subgroup of a population" (Federal Register, Nov 14, 1985, p. 47151).
Paper # 4:
Sauerbrunn BJ, et al. (1965). Chronic fluoride intoxication with fluorotic radiculomyelopathy. Annals of Internal Medicine 63: 1074-1078.
This study reports a case study of a US adult who developed crippling skeletal fluorosis, despite being exposed to water with “just” 2.4-3.5 ppm. In setting its MCL in 1985, the EPA dismissed this study because the patient had experienced chronic excessive thirst. Considering that the goal of the MCL, however, is to protect the most vulnerable subsets of the population, EPA’s rationale for dismissing this finding is unacceptable.
Paper # 5:
Arnala I, et al. (1985). Effects of fluoride on bone in Finland. Histomorphometry of cadaver bone from low and high fluoride areas. Acta Orthopaedica Scandinavica 56(2):161-6.
This study found that bone mineralization defects begin to increase when the fluoride content of water increases above 1.5 ppm. To quote:
“The upper limit for fluoride concentration in drinking water that does not increase the amount of unmineralized bone seems to be roughly 1.5 ppm, according to the results of the drinking water analysis. We should, however, recognize that it is difficult to give a strict value for a safe fluoride concentration in drinking water, because individual susceptibility to fluoride varies.”
Paper # 6:
Ng AHM, et al. (2004). Association between fluoride, magnesium, aluminum and bone quality in renal osteodystrophy. Bone 34: 216-224.
This study is important for at least 2 reasons. It discovered a high accumulation of fluoride (avg = 3,400 ppm in patients with osteomalacia) in the bones of people with kidney disease (in the greater Toronto area). And, as with Arnala (1985), it found a relationship between the accumulated fluoride and bone mineralization defects in the patients.
(NOTE: Since dialysis units now filter out the fluoride from the water, the fact that these patients were on dialysis using fluoridated water should not account for the increased accumulation of fluoride in the bone. Indeed, it has been found that dialysis units which filter out the fluoride, actually serve to reduce the fluoride burden in the body.)
Paper # 7:
Ittel TH, et al. (1992). Effect of fluoride on aluminum-induced bone disease in rats with renal failure. Kidney International 41: 1340-1348.
In light of the recent findings from Ng (2004), as well as the long-held suspicion that fluoride can be a significant contributing factor in aluminum-induced bone disease, this animal study is extremely interesting. The authors found that fluoride exacerbates the aluminum-induced damage to rat bone. Interestingly, the levels of fluoride used in the study are low (20 ppm and 40 ppm in water). Based on my previous analysis of the serum fluoride levels produced in rats at varying water fluoride levels (see Table 7 of my January 29th, 2004 submission), the serum fluoride in these rats would be in the ballpark of 4-8 umol/L. This would be well within the range of serum fluoride in kidney patients living in fluoridated areas (Hanhijavi 1975; Waterhouse 1980; Warady 1989; Torra 1998).
Paper # 8a:
Bo Z, et al. (2003). Distribution and risk assessment of fluoride in drinking water in the West Plain region of Jilin Province, China. Environmental Geochemistry and Health 25: 421-431.
This recent study from China clearly documents that skeletal fluorosis is caused by water supplies exceeding 1 ppm fluoride. The average level of water consumption in the area being studied was estimated to be 3 liters/day, while the average total fluoride exposure was estimated to be 9.4 mg/day. Please note that 9.4 mg/day is a dose that will definitely be exceeded by some people drinking water at EPA’s current MCL for fluoride.
Also note that when the EPA established its fluoride MCL in 1985, it mistakenly believed that skeletal fluorosis only occurred in India and China when the water fluoride concentration exceeded 10 ppm fluoride. To quote:
"EPA notes that crippling skeletal fluorosis, rheumatic attack, pain and stiffness have been observed in a large number of individuals in other countries chronically exposed to fluoride in drinking water at levels of 10 mg/L to 40 mg/L" (Federal Register, Nov 14, 1985, p. 47144).
The most striking problem with this statement by the EPA is not that it has been contradicted by studies published after it was written, but rather, that it had already been contradicted, and frequently so, by seminal research conducted in India during the 40 years preceding the statement.
For instance, in two of the most frequently cited papers on skeletal fluorosis in India, (Singh 1961, 1963) skeletal fluorosis was observed at 1.2 ppm and between 1 and 2 ppm, while Siddiqui (1970) reported skeletal fluorosis at 1.2-1.4 ppm, and Jolly (1970) reported fluorosis at 1.4 ppm.
Many more studies, meanwhile, reported crippling fluorosis above 2 ppm, but far below 10 ppm, including Pandit (1940); Siddiqui (1955); Kumar (1963); and Krishnamachari (1973).
Paper # 8b:
Cao J, et al. (2003). Brick tea fluoride as a main source of adult fluorosis. Food and Chemical Toxicology 41: 535-42.
This study provides a carefully controlled analysis of the doses of fluoride causing crippling (stage III) skeletal fluorosis in Tibet. The average dose among the adults was found to be 12 mg/day. At the EPA’s current MCL of 4 ppm, a portion of the population (people who drink 3+ L/day) will consume more than 12 mg/day from the water-supply alone.
Paper # 9:
Eble DM, et al. (1992). Fluoride concentrations in human and rat bone. Journal of Public Health Dentistry 52: 288-291.
The following study by Eble measured the fluoride content of bones from 24 patients at an orthopaedic hospital in North Carolina. The study is of particular interest considering the glaring scarcity of recent bone fluoride level data from the US. Also, despite the small sampling, the authors found that 4 of the 24 people’s bones had fluoride levels exceeding 3,000 ppm, with 2 of the samples exceeding 3,500 ppm.
To put these figures in perspective, Franke (1975) estimated that the early radiological signs of skeletal fluorosis can be detected when human bone exceeds 3,500 ppm F, while the strength of bone has been found to be reduced in animal studies when the fluoride bone content exceeds 2,500 ppm (Lafage 1995); 2,700 ppm (Mosekilde 1987); and 3,300 ppm (Sogaard 1995).
Paper # 10:
Mihashi M, Tsutsui T. (1996). Clastogenic activity of sodium fluoride to rat vertebral body-derived cells in culture. Mutation Research 368(1):7-13.
This study provides an important follow-up to the NTP’s 1990 fluoride bioassay. Being that the NTP’s bioassay found a statistically significant increase in osteosarcomas in the fluoride exposed male rats, this study sought to determine if fluoride was genotoxic to rat bone. The authors conclude:
“The results indicate that NaF is genotoxic to rat vertebrae, providing a possible mechanism for the vertebrae, as a target organ of NaF carcinogenesis.”
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