March 18, 2002, comments submitted to EPA on Dow AgroSciences petition to establish Fluoride and Sulfuryl fluoride tolerances for a large number (40) of raw and processed foods.
(Federal Register, February 15, 2002)
-See list of tolerances below –
US EPA Docket control number PF-1068
Professor of Chemistry, St. Lawrence U., Canton NY 13617
Tel: 315-229-5853. Fax: 315-379-0448. Email: pconnett@.stlawu.edu
Editor, Waste Not, 82 Judson Street, Canton, NY 13617.
Tel: 315-379-9200. Fax: 315-379-0448. Email: firstname.lastname@example.org
March 18, 2002
Docket control number PF-1068
Public Information and Records Integrity Branch (PIRIB),
Information Resources and Services Division (7502C),
Office of Pesticide Programs (OPP), Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460.
Re: Federal Register: February 15, 2002 (Volume 67, Number 32)] [Notices] [Page 7156-7159]
ENVIRONMENTAL PROTECTION AGENCY [PF-1068; FRL-6822-2]
Before making specific comments on DOW’s proposal, there are a few general comments. We find it extraordinarily cynical that DOW should have first applied for a 3 year Experimental Use Permit (EUP) for the use of sulfuryl fluoride on two food items (walnuts and raisins) and then within 8 days of getting this EUP (February 7, 2002), turn round and apply for tolerances (permanent not experimental) on 40 additional foodstuffs. This smacks of the classic case of the camel getting its nose under the tent flap. Why on earth would you need a EUP for three years, if within 8 days you are seeking a permanent use permit. Did this 3 year experiment only last 8 days? Hopefully, the US EPA is not asleep at the wheel on this.
Our comments on sections B.7 and B.8 of Dow’s submission. These sections are as follows. Our comments follow.
B.7 Metabolite toxicology. Clinical symptoms of acute fluoride poisoning in humans are characterized by nausea, vomiting, diarrhea, abdominal pain, and paresthesia. The frequently cited “probably toxic dose,” the dose which should trigger therapeutic intervention and hospitalization, is 5 mg/kg/bwt calculated for the lowest third percentile of the infant population. Five to 10 grams of sodium fluoride is considered the certainly lethal dose (CLD) for a 70 kg adult (32 to 64 mg fluoride per kg bwt). One-quarter of the CLD can be ingested without producing serious acute toxicity and is known as the safely tolerated dose, i.e., 8 to 16 mg of fluoride per kg of body weight. The Council on Dental Therapeutics of the American Dental Association recommends that “no more than 264 mg of NaF (120 mg F) be dispensed at any one time” in dental treatments to prevent the accidental poisoning of an infant weighing as little as 10 kilograms. EPA (cryolite RED decision, August 1996) determined a maximum concentration limit goal (MCLG) of 0.114 mg/kg/day for fluoride which provides protection from any known or anticipated adverse health effects. The MCLG has been reviewed and supported by the surgeon general. The National Toxicology Program (NTP) has concluded that there was “no evidence” of carcinogenic activity in male or female mice administered sodium fluoride in drinkingwater for 2 years.
B.8 Endocrine disruption. There is no evidence from any studies to suggest that sulfuryl fluoride or fluoride are endocrine disrupters.
1. Fluoride is an Endocrine Disrupter.
Dow is incorrect when it asserts that “There is no evidence from any studies to suggest that sulfuryl fluoride or fluoride are endocrine disrupters.” Below we have listed several lines of evidence which indicates that fluoride inteferes with several hormnal systems. – Note: this short section (in brackets) was inadvertenly left out of our original.]
1.1 The Pineal Gland. The pineal gland is a small endocrine gland located between the two hemispheres of the brain. Its main function involves the production of the hormone melatonin in four enzymatically controlled steps from the naturally occurring amino acid tryptophan. Melatonin has many important regulating roles in the body. It is like a biological clock. It regulates circadian rhythms, sleep patterns, jet lag, the onset of puberty and possibly aging. When researcher Jennifer Luke discovered that the pineal gland is not protected by the blood brain barrier, had a high diffusion rate of blood (second only to the kidney) and it was also a calcifying tissue (i.e. it lays down the same crystals of calcium hydroxy apatite as are produced in the teeth and the bones), she hypothesized that this small tissue would be a magnet for fluoride.
1.2 Fluoride concentrates in the human pineal gland.
When 11 corpses were analyzed Luke found that the levels of fluoride in the crystals in the pineal glands were extremely high (a mean of about 9000 ppm). This research was part of Luke’s Ph.D. thesis and was published in 2001 in the journal Caries Research (Luke, 2001).
1.3 Fluoride lowers the production of melatonin in animal studies.
The second half of Luke’s thesis examined the effect of fluoride on the production of melatonin in Mongolian gerbils. She showed that the levels of a melatonin metabolite excreted in the urine was significantly lowered in high fluoride treated animals, and the animals showed signs of reaching puberty earlier than controls (Luke, 1997).
1.4 Luke’s Ph.D thesis (Luke, 1997) has been sent by us to Dennis McNeilly, Registration Division (7505C), for EPA’s review in November (possibly October) 2001.
1.5 Luke also noted a finding in the health study in the Newburgh-Kingston fluoridation trial (which was not thought significant at the time) that on average the girls in Newburgh started menstruating 5 months earlier than the non-fluoridated Kingston girls (Schlessinger et al, 1956). Thus one of the risks we may be taking by exposing our whole population to fluoride is interfering with delicate regulatory timing processes, from the onset of puberty to the aging process.
1.6 The four step process from tryptophan involves production of the neurotransmitter serotonin. It is conceivable that the production of this important substance is also lowered by the high concentration of fluoride — a well known enzyme inhibitor — in the pineal gland.
1.7 The thyroid gland.
Fluoride also appears to impact the thyroid gland. In the past sodium fluoride tablets have actually been given to patients to relieve the symptoms of hyperthyroidism (Galletti and Joyet, 1958). Independent observers have argued that if fluoride can lower the activity of the thyroid gland of someone suffering from an overactive thyroid gland, it might also reduce the activity of a normal thyroid gland and thus produce the symptoms of hypothyroidism, or it might further exacerbate the problems with those with existing hypothyroidism. Of particular concern, in this respect, is the fact that millions of people in the US are suffering from hypothyroidism. According to the DHHS the range of doses adults receive who live in optimally fluoridated areas is 1.6 to 6.6 mg/day (DHHS, 1991). This range overlaps the range of doses used in the Galletti and Joyet (1958) treatment regime for hyperthyroidism (2.3 – 4.5 mg per day).
1.7.1 Bachinskii et al. (1985) treated 123 people with elevated levels of fluoride(2.3 ppm) in their drinking water. He found that this treatment elevated TSH production, decreased T3 levels, and increased the uptake of radioactive iodide into the thyroid gland. Of the 123 people examined, 47 had normal thyroid function, 43 were hyperthyroid, and 33 were hypothyroid.
1.7.2 EPA published its risk assessment on sulfuryl fluoride in a September 5, 2001, Federal Regster [OPP-301166; FRL-6799-6] and noted:
In chronic (1-2 year) inhalation studies follicular cell hypertrophy in the thyroid gland were observed in dogs and mice.
In subchronic (90-day) inhalation studies follicular cell hypertrophy was noted in the thyroid gland of mice.
In 2-week inhalation studies intermittant tremors and tetany was noted in dogs. Hypoparathyroidism is one of the known causes of tetany.
1.8 Fluoride and G-proteins.
It is now well established in the biochemical literature that fluoride in the presence of trace amounts of aluminum is capable of switching on the G-protein signaling mechanism used for the transmission of signals which arrive at the outside of cells and result in changed activity inside the cell. These messengers include many water soluble hormones, some neurotransmitters, and some growth factors. It would appear that AlF4- can sit in the pocket on the G-protein that is normally occupied by the third phosphate of guanosine triphosphate (GTP). Normally the G-protein is in the “off” position when guanosine diphosphate (GDP) occupies the site; and in the “on” position when GTP occupies the site. However, when the site is occupied by GDP and AlF4-, it looks to the G-protein as if GTP is present, and is thus switched “on.” The GDP (off) – GTP (on) switch is normally triggered when a messenger arrives at the receptor on the outside of the membrane. With AlF4- present the G-protein is switched on without the messenger. It is thus activated without the arrival of the normal messenger. The activated G-protein in turn activates the enzyme (adenyl cyclase) which converts ATP to cyclic AMP, which in turn excites a cascade mechanism resulting in changes inside the cell.
1.9 Fluoride could interfere with many other hormones.
As this G-protein signal (discussed in 1.8) is a key step in the mechanism of action of many water soluble hormones, a number of neurotransmitters and growth factors, this interference by fluoride, in the presence of a trace amount of aluminum, is very worrying indeed. If one goes to the PubMed web and enters fluoride and G-proteins one gets about 800 hits. An important review of this issue and a good starting point for many of these references is provided by Strunecka and Patocka (1999). It is surprising to us that Dow is unaware of this serious biochemical role of fluoride.
Dow’s claim (section B.7) that the NTP concluded “that there was `no evidence’ of carcinogenic activity in male or female mice administered sodium fluoride in drinking water for 2 years” is a misleading, if not a downright deceptive, description of NTP’s long term animal studies with fluoride.
2.1 While is true that the NTP found no increased cancers in the mice study, they found a dose related increase in bone cancer (osteosarcoma) in the male rats. They described this as “equivocal evidence of carcinogenicity.” It disturbs us that Dow should somehow “forget” to put this finding in their discussion of fluoride’s carcinogenic potential.
2.2 Some commentators have attempted to downgrade concern on the male rat finding by stressing that there was no increase in the occurrence in osteosarcomas in the female rats. However, this finding actually follows a fairly consistent set of observations in human studies. This issue has an interesting history which we will now outline.
2.3 The issue of a possible connection between osteosarcoma and fluoridation begins in 1955 with the observations made by Caffey, which are quoted by the National Academy of Sciences (NAS) in their 1977 report. Caffey noted that the Newburg-Kingston study (Schlessinger at al, 1956) indicated a greater incidence of cortical bone defects (which was statistically significant) in the fluoridated community compared to the non-fluoridated one.
2.4 This led the NAS authors to recommend that researchers should check to see if there was an increase in oestosarcomas in fluoridated communities. Note in the following quote that the authors single out studies on MALES under 30 for special attention.
“There was an observation in the Kingston-Newburgh (Ast et al, 1956) study that was considered spurious and has never been followed up. There was a 13.5% incidence of cortical defects in bone in the fluoridated community but only 7.5% in the non-fluoridated community… Caffey (1955) noted that the age, sex, and anatomical distribution of these bone defects are `strikingly’ similar to that of osteogenic sarcoma. While progression of cortical defects to malignancies has not been observed clinically, it would be important to have direct evidence that osteogenic sarcoma rates in males under 30 have not increased with fluoridation.”
2.5 Then in 1990 the study conducted for the National Toxicology Program (NTP), discussed in 2.1 above, found a dose-related increase in osteosarcoma in MALE rats but not female ones.
2.6 In addition, a national cancer survey (the SEER report) found a greater increase in osteosarcomas in young MALES in fluoridated areas. However, Hoover et al (DHHS,1991) from the National Cancer Institute downplayed these findings based on the fact that the cancer incidences were not related to the duration of exposure.
2.7 Then in 1992 Cohn found an increase in osteosarcoma in fluoridated areas in NJ. In three counties he found nearly a seven fold incidence of osetosarcoma in young MALES in fluoridated towns compared to non-fluoridated ones. There was little difference in the rates for females.
2.8 Other studies have not found increases in osteosarcoma in fluoridated communities compared to non-fluoridated ones. However, for a rare cancer it is not unusual to get mixed results. A lot hinges on sample size.
2.9 In our short review of this history we see too many red flags here. A weight of evidence approach should signal caution. In our view, if there is the slightest chance that a few children may succumb to osteosarcoma as a result of early exposure to fluoride, we should not be introducing a new source of fluoride which will increase the load of fluoride to our children.
2.10 We would also note that the osteosarcoms found in the NTP study may not be the only cancers found in this study. Some cancers were removed in a controversial review process (Marcus, 1990). The union which represents the 1500 professional employees of the USD EPA’s DC headquarters is on record as asking for the studies of the various cancers reviewed in this study be reinvestigated by an independent body with no ties to US Government agencies which have actively promoted the addition of fluoride to the public drinking water. (Hirzy, 1999).
3.0 US EPA MCLG for fluoride is not protective.
DOW cites the claim by the US EPA in 1996 that the MCLG for fluoride of 4 ppm of fluoride in water (or 8 mg per day) “provides protection from any known or anticipated adverse health effects.” This claim cannot be supported with an up-to-date, transparent and fully documented review of the current literature. Again, it is both disturbing and somewhat embarassing that neither DOW nor the US EPA appears to be up-to-date on the most recent literature. We will discuss some of these studies below.
3.1 High Dose Hip Fracture studies.
We are fortunate to have some data from high dose human experiments. One of the first was by Riggs et al (1990). There have been several others (Headlund & Gallagher, 1989; Gutteridge et al.; 2002, Bayley et al., 1990). Riggs et al gave 34 mg of fluoride per day for 2-4 years to elderly patients suffering from osteoporosis to see if the fluoride would reverse the loss of bone mineral density which characterizes this disease, and by so doing reduce the incidence of hip fracture. The authors did find an increase bone mineral density in the patients but at the same time, they found that the fluoride made the bones more brittle and more subject to breakage via torsional stress. That such treatments have led to an increase in hip fractures, not a decrease, as hoped and anticipated, provides a highly significant data point. It clearly raises the question that if relatively high doses over a short period of time makes bones more brittle to fracture, what about lower doses over much longer periods of time? What about 70 year exposure to a dose of 1.6 — 6.6 mg per day, that Americans living in optimally fluoridated communities may be exposed to according to the DHHS (1991). And what about the US EPA’s MCLG of 8 mg per day, deemed to provide “protection from any known or anticipated adverse health effects”? Would such a MCLG protect against increased hip fracture?
3.2 Low Dose Hip Fracture Studies.
Since 1990 there have been about 20 investigations into a possible association between living in fluoridated communities and hip fracture in the elderly. Just over half have found a greater incidence of hip fracture in the fluoridated communities. Many of these studies (as with many of the studies which compare dental decay rates) are limited because they are ecological in nature with no data on individual exposure. Two recent studies may have helped to resolve this issue: one by Li et al (2001) in China and the other by Alarcon-Herrera et al (2001) in Mexico.
3.3 Li et al (2001) looked at hip fracture rates in elderly residents in six Chinese villages with different levels of fluoride in their well water. They determined a relative risk ratio for each of six villages taking the level of hip fractures in the village with 1 ppm as their reference. While they found little difference in the hip fracture rates in the villages less than 1 ppm, they found that the rates almost doubled when the levels of fluoride went above 1.5 ppm and tripled when they went over 4.5 ppm. This apparent dose response adds a great deal of weight to this ecological study. The doubling of the hip fracture rates above 1.5 ppm and the tripling of the hip fracture rates at levels over 4.5 ppm, puts into serious question the safety of the US EPA MCLG of 4 ppm.
3.4 Alarcon-Herrera et al (2001) in a study conducted in Mexico found a linear correlation between the severity of dental fluorosis in both children and adults and the incidence of bone fracture. I think this paper is exceptionally important not only for this particular finding but also in providing an elegant way of using a biomarker for fluoride exposure in children. It has been known since Dean’s studies in the 1930’s (see also Heller et al ,1997) that there is a strong linear correlation between the level of fluoride in drinking water and the severity of dental fluorosis in children. This biomarker could be used to investigate other childhood concerns possibly related to fluoride exposure, such as IQ deficits; hyperactivity; melatonin levels; earlier onset of puberty, and thyroid function.
3.5 Millions of people living in India, China and other parts of the world with naturally high levels of fluoride in their drinking water (2-20 ppm) suffer from skeletal fluorosis. While not many cases of skeletal fluorosis have been documented in the US (possibly because few doctors are trained to recognize the disease) much of the discussion has been focussed on the stage of the disease which produces crippling effects. It was on this end point, for example, that the US EPA set its MCLG for fluoride at 4 ppm. However, there are several stages of this disease and the early stages are less obvious to the untrained observer. What is particularly disturbing is that the earliest clinical symptoms of the disease are identical to the early symptoms of oestoarthritis and other forms of arthritis. With over 40 million Americans suffering from various forms of arthritis, the possibility that fluoride may be causing osteoarthritis or exacerbating it, becomes a very important question. This is especially so since the cause of osteoarthritis has not been identified; it is usually explained as being part of the aging process. We have to ask whether part of this “aging process” is the steady accumulation of fluoride in our bones.
3.6 Often studies from India are dismissed on the basis that the levels of fluoride in the drinking water are high and not comparable to the levels in America or in American regulations. However a recent study by Michael et al. (1996) found
Serum thyroixine (T4): Levels showed a significant increase (P < 0.001) compared to control.
Serum catechlolamines: The serum adrenalin and nor-adrenalin levels increased significantly in fluorotic individuals (P < 0.001) compared to controls.
Serum protein and calcium: Levels of the endemic population showed a highly significant decrease (p < 0.001) as compared to the control.
The levels reported by Michael et al. in the drinking water ranged from 1.0 to 6.53 ppm. It should be noted that 85% of the villages studied here had water levels BELOW the EPA’s MCLG of 4 ppm:
50 % had F content within the range of 2 – 4 ppm
35% had F content below 2 ppm
15% had F levels above 4 ppm
Michael et al. also reported that :
“74% of the individuals showed slight to severe mottling of teeth. 59% had stiffness of spinal cord. Other skeletal problems such as stiff hands and fingers (60%), stiffness of legs and joints (65%) were also common…”
3.7 The fluoride bone levels (ashed) associated with the pre-clinical phase of skeletal fluorosis are in the range 3,500-5,500 ppm (DHHS,1991, Table 23). It would be nice to know how close we are getting to these levels with lifetime exposure to fluoride from many sources. Unfortunately, despite its heavy promotion of water fluoridation and the millions of dollars spent on dental research, the US PHS has never sought fit to do the most elementary thing of preparing a comprehensive data base on fluoride bone levels in the US as a function of age, sex, race, location, fluoridation status, disease status, diet or anything else.
3.8 According to the National Research Council (1993): “Crippling skeletal fluorosis might occur in people who have ingested 10-20 mg of fluoride per day for 10-20 years” and according to the DHHS (1991) the range of adult daily dose in the US, in optimally fluoridated areas, is 1.6 – 6.6 mg per day. If we apply simple arithmatic to these figures (i.e. 1.6 to 6.6 mg per day) someone in the middle of the range might reach severe skeletal fluorosis in about 60 years. Furthermore, they might reach the milder symptoms, which are similar to the symptoms experienced in osteoarthritis -aching bones and joints – in less time than this. Someone receiving the 8 mg per day deemed protective by the US EPA would reach the early symptoms still earlier.
3.9 The statement by the National Research Council (1993): “Crippling skeletal fluorosis might occur in people who have ingested 10-20 mg of fluoride per day for 10-20 years” refutes the claim by Dow [Section E.1] that “there is no directly applicable scientific documentation of adverse medical effects at levels of fluorine below 0.23 mg/kg/day.” Since for a 70 kg adult 0.23 mg/kg/day translates to 16 mg a day.
4. Fertility and Reproductive Effects.
Freni (1994) found lowered fertility in US counties which have fluoride levels at 3 ppm or higher. There has been some criticism of Freni’s methodology, but we have not seen any of it which has been peer reviewed and published. Should Freni’s finding be substantiated it would challenge the notion that 4 ppm is protective with respect to this serious outcome. Why was this issue not discussed by DOW?
4.1 Susheela AK and Jethanandani (1996) found lowered testosterone levels in patients with skeletal fluorosis in India. In a series of animal experiments both Sushella, Chinoy and others have found that fluoride lowers the testosterone levels and the production and quality of sperm (Chinoy and Sequeira, 1989; Chinoy et al., 1991; Chinoy and Narayana, 1994; Kumar and Sushella, 1994). See TABLE 7 for abstracts.
5. Impacts on the Central Nervous System.
Since the middle 1990s there have been several important studies which have probed fluoride’s possible impact on the brain. Mullenix (1995) demonstrated that rats treated prenatally with fluoride showed behavior patterns associated with hyperactivity and rats dosed after birth showed hypoactivity. Guan et al. (1998) showed that membrane lipids in rat brain were impacted by chronic fluorosis.
5.1 Several studies in China (Lee et al. 1985; Zhao et al. 1996; and Lu et al. 2000) have shown the possible impact of high background fluoride (possibly in the presence of low iodide, Zhao, 1998) on children’s IQ. One of those that we have examined is the work by Zhao et al (1996) who found an approximate 5-10 point IQ deficit in children from a community with water containing 4 ppm natural fluoride compared to one containing 1 ppm. Since we fluoridate at 1 ppm, and the EPA’s MCLG for fluoride is 4 ppm, this paper is of considerable concern.
5.2 An indication of how oblivious American authorities are to these possible dangers, is the fact that some schools in the US add 4.5 ppm of fluoride to their drinking water systems. For example, seventy-five (75) schools in Indiana fluoridate their drinking water systems at 4.5 ppm; sixty-one (61) schools (or communities) in North Carolina fluoridate their drinking water systems at 4.5 ppm; and sixty-four (64) schools in Kentucky fluoridate their drinking water systems at 4.0 ppm (US DHHS,1993). See TABLE 1.
5.3 Varner et al (1998) exposed rats to fluoride in their drinking water for one year. What was remarkable about this work is how low the concentrations were that caused damage. Both AlF3 (aluminum fluoride) and NaF (sodium fluoride) given to the animals at the level of 1 ppm fluoride (the same level generally used in public drinking water) in their doubly distilled de-ionized drinking water caused both kidney and brain damage, an accumulation of aluminum into the brain and the formation of amyloid plagues which are associated with Alzheimer’s disease. Apparently, this is the third time that Isaacson and his co-workers have found effects on the brain at these remarkably low levels.
5.4 As a result of Varner’s work aluminum fluoride was recently nominated by the Environmental Protection Agency and National Institute of Environmental Health Sciences for testing by the National Toxicology Program. According to the EPA and NIEHS, aluminum fluoride is a “drinking water contaminant” with “known neurotoxicity” and a “high health research priority.” If fluoride is added to water which contains aluminum, than aluminum fluoride complexes will form (BNA, 2000, see http://www.fluoridealert.org/alum-fluoride.htm). We would add that if some of the fruits and vegetables with the fluoride residues proposed in DOW’s application were cooked in aluminum saucepans, this too could lead to the formation of aluminum fluoride complexes.
6. Summary of Health Concerns on Fluoride.
It should be clear from the above sections (1 – 5) that DOW’s claim that an MCLG of 4 ppm which projects to a 0.114 mg/kg bodyweight dose per day, or 8 mg per day for a 70 kg adult, is “protective with respect to known and anticipated health effects” is not supported by an independent review of the literature. Dow’s claim neglects the studies which pertain to neurobehaviour; the thyroid gland; the pineal gland; increasing hardness and brittleness of the bone; increased risk of hip fracture; pain in the bone and joints; lowering of fertility, and osteosarcoma in young men. To make matters even worse, DOW, later on in their submission (section E.1), claims that “there is no directly applicable scientific documentation of adverse medical effects at levels of fluorine below 0.23 mg/kg/day.” This figure translates to a dose of 16 mg of fluoride per day for a 70 kg adult. If the claim that 8 mg per day was safe is unsupportable, then the claim that 16 mg is safe is doubly unsupportable!
7 With respect to Sulfuryl fluoride we also have some serious concerns.
7.1 Impacts on the Brain.
7.2 EPA’s risk assessment of sulfuryl fluoride published in the Federal Register on September 5, 2001 (66 FR 46415) notes the following impacts on the brain:
In 2-week inhalation studies: In rabbits, the primary target organ was the brain, in which malacia (necrosis) and vacuolation were observed in the cerebrum.
In subchronic (90-day) inhalation studies in rats, dogs, rabbits and mice, the brain was the major target organ. Malacia and/or vacuolation were observed in the white matter of the brain in all four species. The portions of the brain most often affected were the caudate-putamen nucleus in the basal ganglia, the white fiber tracts in the internal and external capsules, and the globus pallidus of the cerebrum. In dogs and rabbits, clinical signs of neurotoxicity (including tremors, tetany, incoordination, convulsions and/or hind limb paralysis) were also observed.
In chronic (1-2 year) inhalation studies in rats, dogs and mice, target organs were the same as in the 90-day studies… Other treatment-related effects in rats included effects in the brain (vacuolation of the cerebrum and thalamus/hypothalamus).. In dogs and mice, increased mortalities, malacia and/or vacuolation in the white matter in the brain…
Following two exposures on consecutive days for 6 hours/day at 300 ppm of sulfuryl fluoride (354 mg/kg/day), no treatment-related neurotoxic effects were noted. In a 90-day study, changes in some EEG patterns were observed at 100 ppm (80 mg/kg/day) and in several additional patterns at 300 ppm (240 mg/kg/day). Vacuolation of the white matter in the cerebrum was also observed at 300 ppm in this study.
In a 2-generation reproduction inhalation study in rats, vacuolation of the white matter in the brain, pathology in the lungs (pale, gray foci; increased alveolar macrophages) and decreased body weights were observed in the parental animals.
7.3 Brain White Matter and the Susceptibility of Young Children.
EPA noted in its September 5, 2001, risk assessment of sulfuryl fluoride that brain white matter was a major target in several of the animal studies (rats, dogs, rabbits, mice). EPA noted in its Sulfuryl fluoride RED document of 1992:
“Very young children may be more susceptible than adults to sulfuryl fluoride neurotoxicity because the developing brain may be more vulnerable to chemical injury (p 15).”
7.4 According to Filley (2001) white matter development in young children differs “significantly” from gray matter:
“Gray matter and white matter differ significantly in their patterns of development. Nerve cells begin to develop early in gestation, and the entire complement of central nervous system neurons is formed before birth (Nolte, 1999). The embryonic development of gray matter involves continual pruning of inessential neurons by programmed cell death and the simultaneous establishment of synaptic contacts between the ones that remain (Kandel et al., 2000). In contrast, the white matter does not begin to form until the middle trimester of gestation (Nolte, 1999). The process is only partially completed at birth, and even by 2 years of age, it is still just 90% complete (Byrd et al., 1993). The remainder of myelination then requires many years (Yakovlev and Lecours, 1967; Klingberg et al., 1999; Fig. 3-1). The exact duration of this proces is unclear, but recent evidence from a series of normal brains studied postmortem suggests that myelination proceeds throughout the end of the 6th decade (Benes et al., 1994) (p 33).”
7.5 Of some concern is the fact that when the mottling of the teeth was observed (a known effect of the free fluoride ion) in sulfuryl fluoride animal experiments, vacuolation of the white matter of the brain was found also. For example:
R.E.D. Facts (1992). “Administration of sulfuryl fluoride by inhalation for 6 hours/day for 90 days to rabbits at doses of 30, 100, or 300 ppm (11, 38, or 114 mg/kg/day) resulted in similar signs of toxicity although brain lesions occurred at lower levels. The NOEL was 30 ppm. The LEL was 100 ppm based on decreased body weights, decreased liver weight and mottling of the teeth (M,F), and microscopic vacuolation of the white matter of the brain (F). In addition, at 300 ppm (M,F) there was alveolar histiocytosis, histologic changes in the nasal epithelium, and microscopic malacia to vacuolation of the internal and external capsules, putamen, and globus pallidus of the brain (MRID # 408909-01).” http://www.epa.gov/oppsrrd1/REDs/old_reds/sulfuryl_fluoride.pdf
7.6 In a search for “white matter” at the EPA Office of Pesticide Programs search site( http://www.epa.gov/pesticides/search.htm ) only six pesticides were cited, four of these were fluorinated: Sulfuryl fluoride, Fluazinam (an organofluorine pesticide); Bromethalin (an organofluorine rodenticide); and Chlorfenapyr (an organofluorine pesticide). The other two were Hexachlorophene and Bensulfide. See TABLE 2 for a review of the search.
7.7 For Sulfuryl fluoride and the organofluorine pesticides cited above (Fluazinam, Bromethalin, Chlorfenapyr) animal studies reveal a disruption of the myelin – see TABLE 3.
According to Filley (2001):
“The clinical significance of the sequence of brain myelination has long been debated. Flechsig (1901) first speculated that myelination reflected functional maturity of the cerebral areas involved, and the observations of Yakovlev and Lecours (1967) supported this idea. However, the relative importance of white matter versus gray matter development has not been entirely clear. More recently, neuroadiologists have increasingly interpreted delayed mylination on MRI as indicating a neurologic abnormality (Byrd et al., 1993). In clinical studies, there have been many suggestions that intact white matter contributes to cognitive development. In MRI studies of children with congenital hydrocephalus, for example, cognitive impairment has been correlated with delayed myelination (van der Knapp et al., 1991) and with reduced size of the corpus callosum and other cerebral white matter tracts (Fletcher et al., 1992).
“One of the intriguing notions to arise from study of this area is the possibility that the acquisition of the mature personality in young adulthood depends to a substantial extent on frontal lobe myelination (Filley, 1998). Normal personality development requires the acquisition of traits such as reasoning, impulse control, and judgement that are traditionally associated with frontal lobe function. Because myelination of the frontal lobe occurs quite late in development – at a time when gray matter is relatively stable – the arrival of the adult personality may require the completion of this myelogenetic phase. Moreover, subtle modifications in personality with later adulthood may conceivably relate to continuing myelnation in the 5th and 6th decades (Benes et al., 1994). The understanding of these potential correlations could help establish a foundation for considering the neural organization of personality throughout the life span (p 33-34).
“A wide range of syndromes involving both cognitive decline and emotional dysfunction has been linked with structural involvement of the brain white matter. Clinical observations of patients with white matter disorders generate the essential data to support this claim. Much additional information has been gathered with the help of magnetic resonance imaging (MRI), a powerful neuroimaging technique that has provided unprecedented views of the white matter and permitted correlations with neurobehavioral syndromes. These syndromes may equal or surpass in clinical importance the various deficits in motor and sensory function of white matter lesions well known from classical neurology. Whereas caution is still appropriate in assessing the neurobehavioural importance of white matter changes, it is no longer possible to ignore them. (p 3-4)É
“Early clinical features of cerebral white matter involvement typically include confusion, inattention, memory dysfunction, and personality changeÉ Measures of attention, cognitive speed, memory retrieval, visuopatial skills, and executive function are likely to be most sensitive to subtle white matter dysfunction. In contrast to disorders primarily involving the cortex, higher cerebral functions such as language, praxis, and perception are uncommonly affected; the usual preservation of language is an important point because affected individuals may display normal language and thus appear cognitively intact, when in fact they have significant deficits in other neurobehavioral domains (p 249).
7.8 See TABLE 4 and TABLE 5 for a list of diseases and disorders associated with white matter disruption.
7.9 If we take into consideration both Varner et al. (1998) and the impacts on white matter discussed above a simple hypothesis suggests itself. Fluorine is particularly threatening to the brain, if it can be carried there, either in the form of a metal fluoride complex (eg. AlF3) or as a fluorinated substance (eg, sulfuryl fluoride or one of the organofluorines noted above). It might turn out that it is the intact complex or the intact molecule which causes the problem. But it also might turn out that it is the release of the free fluoride ion once the substance has got into the brain that causes the problem. Or both. Clearly a much more thoughtful and comprehensive analysis of this issue demands the attention of the regulatory agencies before they approve the use of sulfuryl fluoride in or on foodstuffs which could be consumed by humans, especially by young children. With so much uncertainty in this area it would be cavalier in our view to ascribe a tolerance which is considered “safe” or acceptable. At this stage in our knowledge the only appropriate approach is to assume a safety level of zero for sulfuryl fluoride on any foodstuff that is going to be consumed by infants or young children. The value of zero can be assured by not permitting the use of sulfuryl fluoride as a fumigant on these foodstuffs.
8 Faith in the U.S. Surgeon General or Review of the Literature
According to DOW the 4 ppm MCLG has been “reviewed and supported by the US Surgeon General.” However, it would be both unacceptable and unscientific to use such a statement as an excuse not to review the most up-to-date literature on fluoride’s toxicity and mechanism of action, discussed above (Sections 1 – 6). Even the US Surgeon General has to support his claims and pronouncements with scientific studies. Moreover, it is important to put the position of the US Surgeon General into some kind of historical perspective.
8.1 Ever since the US Public Health Service endorsed fluoridation of the public water supplies in 1950, before one single fluoridation trial had been completed, each reigning Surgeon General has been expected to be the poster child for this practice. They are used in the same way that Michael Jordan is used to promote Nike sneakers.
8.2 It is highly questionable whether such statements or endorsements from a long line of US Surgeon Generals since 1950 have been based upon their own personal review of the literature. It is far more likely that their staff pass onto them the findings of various agencies within the US PHS. Based upon what we know of the recent performance of such agencies this is not a reliable source for up-to-date information. For example, the CDC in its October 1999 MMWR report, which was the basis for its much quoted claim that fluoridation is one of the top 10 medical achievements of the twentieth century, was six years out of date on the health studies it cited to dismiss any health effects associated with water fluoridation. For a blow by blow critique of the CDC study see our review (Connett P and Connett M, 2000).
9 Children overexposed to fluoride in the United States.
Before we turn to considering Dow’s calculations about exposure to fluoride from the use of sulfuryl fluoride as a fumigant on foodstuffs it is important to stress that there is important evidence that indicates that a fair percentage of the children in the U.S. are already overexposed to fluoride. This evidence is the level of dental fluorosis. We fully discuss this matter in Seciton 14.
10 OUR COMMENTS ON SECTION C.
We will first print out DOW’s comments:
C. Aggregate Exposure
1. Dietary exposure. The Dietary Exposure Evaluation Model (DEEM), version 7.73, of Novigen Sciences, Inc. was used to estimate the dietary exposure to the U.S. population and critical sub-populations resulting from the use of sulfuryl fluoride under the conditions proposed. The highest potential chronic exposures to sulfuryl fluoride was to children ages 1 to 6 years resulting from the consumption of treated commodities totaling 0.000106 mg/kg/bwt/day. Likewise, the highest potential chronic exposure to fluoride was to children ages 1 to 6 years with a highest estimated exposure of 0.002419 mg/kg/bwt/day. i. Food. Food tolerances as inorganic fluorine compounds exist to support the uses of cryolite (insecticide) on various food and feed commodities in the U.S. EPA, in the 1996 cryolite RED document, conservatively estimates that the “high-end” dietary exposures to fluoride due to all sources and routes (including the fluorination of water and the potential for fluoride residues resulting from the uses of cryolite) are approximately 0.085 mg/kg/bwt/day. No toxicological endpoint attributable to a single exposure was identified in the available toxicology studies on sulfuryl fluoride or inorganic fluoride that would be applicable for an acute dietary exposure.
10.1 The way that DOW presents this data is not helpful for the general public which does not have access to the DEEM model of Novigen Sciences, Inc. Unless the US EPA is prepared to leave these matters in the hands of private consultants or some other priesthood, they should insist that DOW make the raw data available so that their calculations may be checked.
10.2 In our view what was needed was a table of the range of daily or yearly consumptions of the 40 foodstuffs in question for the various age ranges in the population, or at least a reference to where such a table can be easily located and accessed.
10.3 DOW’s reporting the data as a dose in terms of mg per kg bodyweight per day is not helpful without specifying the bodyweights for the ages involved.
10.4 We request that the US EPA insists that DOW present their data in the following clear and easily checkable steps:
Step 1. How many mg per kg in each food stuff, ie, the tolerances.
Step 2 How many kg of each foodstuff consumed per age group (this should be reported as a range)
Step 3 The range of total mg per day consumed for each age range
Step 4 The average bodyweight for each age group
Step 5 The range of total dose in terms of mg per kg bodyweight per day for each age group.
10.5 DOW states that the US EPA estimated in 1996 that “the “high end” dietary exposure to fluoride due to all sources and routes (including fluorination (sic) of water and the potential for fluoride residues resulting from the uses of cryolite) are approximately 0.085 mg/kg/bwt/day” this would translate to a daily dose of 6 mg for fluoride for a 70 kg adult. In our view, this is far too close to the MCLG of 8 mg per day, especially if the US EPA did not include all sources of fluoride exposure such as the wide range of dental products; exposure via mechanically deboned meat products; vitamin tablets containing fluoride; bone meal dietary supplements; fluorinated pharmaceuticals which may metabolize to free fluoride ion and exposure to fluoride air pollution via inhalation and home grown food (HF is the number six in air pollutants in the US).
10.6 It is particularly important that when the US EPA re-estimates the total dose of fluoride for various age ranges of the US population that they include an estimate of fluoride exposure through inhalation and through food contaminated by air pollution. To this end in TABLE 6 we have included the TRI releases by state. However it should be remembered that not all industries or emissions are included in the TRI.
11 OUR COMMENTS ON SECTION D.
DOW STATES: D. Cumulative Effects The primary degradation product of sulfuryl fluoride is fluoride. The toxicity of fluoride in various forms has been extensively reviewed and is used as an additive in treated water supplies, toothpastes, mouth rinses, and other treatments for the prevention of dental caries. It is also prescribed in therapeutic amounts for the treatment of osteoporosis. Fluoride is naturally present in both food and water in varying amounts, and has been added to public water supplies to fight dental caries. The recommended concentration of fluoride (usually as fluorosilicic acid) in treated water supplies is 0.8 ppm to 1.0 ppm. The third report on nutrition monitoring in the United States says that food contributes only small amounts of fluoride and monitoring the diet for fluoride intake is not very useful for current public health concerns. The sub-population most susceptible to fluoride is children. For this reason a number of studies have attempted to quantify the fluoride intake from a variety of sources. The total daily intake of fluoride from water (used to prepare formula, juices, and other foods) for infants ages birth to 9 months ranged to 1.73 mg with means from 0.29 to 0.38 mg. Assuming a body weight of 10 kg, these amounts are equivalent to 0.03 to 0.04 mg/kg/day. These levels of dietary exposure in combination with the potential dietary exposures that the proposed uses of ProFume would represent (chronic dietary exposures of 0.002419 mg/kg/bwt/day) are considerably lower than EPA’s MCLG for fluoride of .114 mg/kg/bwt/day.
11.1 We do not understand why DOW should restrict its concern here to a children aged 0 to 9 months. Exposure to older children is also of concern especially young boys whose bones are growing very fast.
11. 2 Nor do we understand why the exposure is restricted to exposure from water. Regrettably pediatricians are still prescribing fluoride drops to babies and older children are exposed to fluoride through dental products, especially those who can’t control their swallowing reflex.
11.3 However, DOW’s statement that the fluoride exposure to young children up to 9 months, ranged up to 1.73 mg was not converted (unlike the mean values) to mg/kg/day. Had they done so using the same bodyweight of 10 kg, they would have found that the dose ranged up to 0.173 mg/kg/day. This figure of 0.173 mg/kg/day is OVER the EPA’s MCLG for fluoride (i.e., 0.114 mg/kg/day). In other words even taking the EPA’s lax standards at their face value, DOW’s own data indicate that some infants up to the age of 9 months are already being overexposed to fluoride. This should clearly rule out any further addition of fluoride to foodstuffs that might be fed to babies up to 9 months, which includes a number of the foodstuffs for which DOW is seeking tolerances.
12 OUR COMMENTS ON SECTION E.
E. Safety Determination
1. U.S. population. Aggregate risk from exposure to sulfuryl fluoride would be minimal because of its rapid dissipation from any fumigated commodity and because it is not expected to be present at the time of food consumption. The sulfuryl fluoride residues in fumigated foods are expected to be non-detectable at the point of food consumption. Furthermore, if residues were considered as high as what is found immediately following the 24-hour aeration period, the margin of exposure to the most sensitive population (children) is estimated to be greater than 80,000 for chronic exposures. Exposure to fluoride, the residue of interest for sulfuryl fluoride, can occur from foods, water, and dental treatments. The additional fluoride residues in some commodities fumigated with sulfuryl fluoride are indistinguishable from the natural levels of fluoride already present and would therefore also fall within EPA’s threshold of regulation policy. Alternatively, fluoride in other commodities are expected to contribute to the fluoride that is ingested, but at levels far below other sources, especially treated water and dentrifices. Chronic exposure to fluoride resulting from the proposed uses of ProFume (0.002419 mg/kg/day) is much lower than EPA’s MCLG of 0.114 mg/kg/bwt/day calculated for exposure to fluorinated water. In addition, there is no directly applicable scientific documentation of adverse medical effects at levels of fluorine below 0.23 mg/kg/day.
2. Infants and children. Chronic exposure to fluoride from the consumption of ProFume treated commodities would be approximately 0.002419 mg/kg/day for a child age 1 to 6 years. This value is much lower than EPA’s MCLG of 0.114 mg/kg/bwt/day calculated for exposure to fluorinated water.
12.1 Here DOW makes the classic mistake of DIVIDING the incremental exposure to fluoride (from their proposed action) to the existing background exposure, when what they should be doing is ADDING the incremental exposure (for various age groups) to the existing background exposure.
12.2 What is of interest here is the TOTAL exposure to fluoride. This is what should be compared with the EPA’s MCLG of 0.114 mg/kgbw/day (8 mg per day for a 70 kg adult or 1.14 mg/day for a 10 kg infant), as lax as that may be.
12.3 We have already commented on DOW’s preposterous assertion that , ” there is no directly applicable scientific documentation of adverse medical effects at levels of fluorine below 0.23 mg/kg/day” in section 3.14 above.
13 OUR CONCLUSIONS.
13.1 Our initial concern about fluoride’s toxicity came from our study of the water fluoridation controversy. We were reluctant to get involved in this issue because of two things, a) we like most Americans have been brought up to believe that fluoride is a benign substance of great benefit to teeth and b) we both have heavy time commitments to other activities.
13.2 However, once we were persuaded to review this issue some six years ago, we were appalled by several things: a) that the benefits of water fluoridation had been greatly exaggerated (Diesendorf, 1986; Yiamouyiannis, 1990; Colquhoun, 1987 and 1997; Locker, 1999; York Review, 2000). b) that the risks from exposure to fluoride have been greatly underestimated by those promoting fluoridation and c) the level of scientific knowledge and integrity on this issue of those US government agencies which should be protecting our health in this matter has been atrocious (CDC, 1999; CDC, 2001). Science has had to take second seat to the continued promotion of this discredited practice at all costs. It was precisely this substitute of PR science for physical science by the USEPA on this matter which prompted the union which represents many of the professionals who work at their Washington, DC headquarters to come out and publicly oppose water fluoridation (Hirzy, 1999).
13.3 What is abundantly clear to anyone with an open mind, who studies the literature on this issue is that children in the US are being overexposed to fluoride. This conclusion can be derived simply by calculating the various and multiple sources of fluoride a child is exposed to today. Another way of reaching the same conclusion is to examine the level of dental fluorosis in this country, which we discuss below. Under these circumstances no US agency should be countenancing for one moment the addition of still more fluoride to a child’s diet. It is unthinkable and it is undefendable by any honest regulatory scientific methodology.
14 Dental fluorosis is a biomarker for overexposre to fluoride.
One effect of fluoride which is not denied by even the most avid promoter of fluoridation is “dental fluorosis.” In 1931 it was shown that “mottling of the enamel,” which ranges from very small white specks to more noticeable white specks covering larger areas of the teeth, then to orange and brown stains and finally pitting of the teeth, was caused by naturally high levels of fluoride in the water (above 1 ppm). We now know that this is a systemic effect. The fluoride has to be ingested before the permanent teeth have erupted.
14.1 The early researchers on this issue reported that even though children in these areas had this “dental fluorosis” their teeth seemed to have fewer cavities. It was H. Trendley Dean of the US Public Health Service who set out to find if there was a level of fluoride in the water, which reduced dental decay while not causing too much dental fluorosis. He settled on the so called “optimal level” of 1 ppm , which he argued would reduce dental decay but would limit dental fluorosis, in its mildest form, to about 10% of the population.
14.2 This hypothesis was put to the test in several trials in the US and Canada which began in 1945. These were in Grand Rapids (the control city was Muskegon) Michigan; Newburgh (the control city was Kingston) New York; Brantford (the control city was Sarnia) Ontario and Evanston (Illinois). These trials were designed to last for at least 10 years, but within a few years people were reporting such dramatic results that the US PHS was persuaded to endorse fluoridation in 1950 before one single trial had been completed. The late Dr. Philip Sutton heavily criticized the methodology used in these early trials (Sutton, 1959, 1960 and 1996) and there has been no satisfactory rebuttal to these criticisms from those who promote compulsory fluoridation.
14.3 Since these trials began the number of sources of fluoride that we are exposed on a daily basis has dramatically increased. We get it from water; from food and beverages processed with fluoridated water, from toothpaste, mouthwashes and other dental products; from pesticide residues and from air pollution. So while, the original goal of the program was to provide approximately 1 mg per day (assuming that we drink about a liter of water a day), today the DHHS estimates that an adult living in an optimally fluoridated area (0.7 – 1.2 ppm) gets between 1.6 and 6.6 mg per day (DHHS, 1991).
14.4 The clearest evidence that we are getting more fluoride today than we were in 1945, is the way that dental fluorosis figures have rocketed.
14.5 The largest survey of dental fluorosis carried out in the USA was performed by Heller et al (1997). They found that in optimally fluoridated communities (0.7 – 1.2 ppm F) the percentage of children with dental fluorosis on at least two teeth was 29.9%. Not only have we seen a threefold increase over the original 10% goal, but the dental fluorosis being observed is not all in its mildest form. Moroever, Heller’s survey is based on data collected in 1986-87, and there is every reason to believe that the percentage of people impacted by dental fluorosis has increased since then. In some communities in the US the incidences of dental fluorosis have been found to exceed 50% (Williams, 1990; Lalumandier, 1995 and Morgan, 1998). In one city in Georgia it impacts 80% of the children.
14.6 The recent York Review (discussed above) estimated that fluorosis impacts (on an average basis worldwide) 48% of the population when the water is fluoridated at the optimal level.
14.7 Thus, based upon these alarming dental fluorosis* figures it is clear that we are over-exposing our children to fluoride. Based upon this and the other arguments presented above we call upon the US EPA to deny DOW’s request for fluoride tolerances. Instead, we urge DOW and other chemical companies to seek a fumigant which neither contributes to ozone depletion, like methyl bromide, nor presents an unacceptable toxic burden on our population.
* Frequently fluoridation promoters dismiss this outcome as merely a “cosmetic” effect. In our view, this is simply a political maneuver to protect the fluoridation program at all costs. Paraphrasing what one commentator said about this, it is like describing the blue line that appears on the gum in some cases of lead poisoning as a merely a “cosmetic effect.” For a scientist, both the blue line on the gum in the case of lead poisoning and the white or colored specks on the tooth enamel in the case of fluoride exposure, is the first visible sign that the toxic substance in question has had its first visible toxic effect on the body. It should raise the question of other effects which have taken place but which do not have visible signs. It should also raise the question of the mechanism by which fluoride achieves this end point. DenBesten (1997) provides some evidence that dental fluorosis is caused by the inhibition of an enzyme (a protease) which removes the last little bit of protein from between the mineral (i.e. calcium hydroxy apatite) prisms before they fuse to form the smooth enamel surface. It is the failure to remove this protein which causes the gaps in the enamel surface. The important question to ask from the toxicological point of view is: if fluoride is able to poison this enzyme in the growing tooth what other enzymes in the body can it poison? For example, what enzymes in the bone may it poison? What enzymes in other tissues may it poison? The work of Jennifer Luke on the pineal gland, bears on this last question (see sections above). In 1981 John Emsley threw more light on fluoride’s mechanism of action when he showed that fluoride forms a strong hydrogen bond with the amide function. This not only explains why fluoride inhibits many enzymes but also indicates why it may interfere with DNA whose structure and function hinges on hydrogen bonds (Emsley, 1981).
The following Tables appear at the end of the references.
Table 1: Some Fluoridated School Drinking Water Systems
Table 2: Results from a March 18, 2002, search of the EPA Office of Pesticide Program site for “White Matter”
Table 3: Myelination Effects / Fluorinated Pesticides
Table 4: White Matter Disorders and Diseases.
Table 5: White Matter associated Traumatic Disorders, Neoplasms and Hydrocephalus.
Table 6: By State: 1999 TRI Hydrogen Fluoride air releases and percentage of population with fluoridated public drinking water 1992-2000.
Table 7: Reproductive Effects of Fluoride
Alarcon-Herrera MT et al. (2001). Well water fluoride, dental fluorosis, and bone fractures in the Guadaina Valley of Mexico. Fluoride, 34(2):138-48.
Bachinskii PP et al. (1985) Action of the body fluorine of healthy persons and thyroidopathy patients on the function of hypophyseal-thyroid system. Probl Endokrinol (Mosk) 31(6):25-9.
Bayley TA et al. (1990). Fluoride-induced fractures: relation to osteogenic effect. J Bone Miner Res. Mar;5 Suppl 1:S217-22.
Benes FM et al. (1994). Myelination of a key relay zone in the hippocampal formation occurs in the human brain durng childhood, adolescence, and adulthood. Arch Gen Psychiatry; 51: 477-484. (Cited by Filley, 2001).
Brunelle JA and Carlos JP (1990). J. Dent. Res 69, (Special edition), 723-727.
Byrd SE et al. (1993). White matter of the brain: maturation and myeliation on magnetic resonance in infants and children. Neuroimaging Clin N Am 3:247-266. (Cited by Filley, 2001).
Calderon J et al. (2000). Influence of fluoride exposure on reaction time and visuospatial organization in children. Epidemiology 11(4): S153.
CDC. Centers for Disease Control and Prevention (2001). Recommendations for using fluoride to prevent and control dental caries in the United States. MMWR. August 17, 50(RR14):1-42.
CDC. Centers for Disease Control and Prevention (1999). Achievements in public health, 1900-1999: fluoridation of drinking water to prevent dental caries. MMWR, 48(41): 933-940.
Chinoy NJ, Sequeira E (1989). Effects of fluoride on the histoarchitecture of reproductive organs of the male mouse. Reprod Toxicol, 3(4):261-7
Chinoy NJ et al. (1991). Microdose vasal injection of sodium fluoride in the rat. Reprod Toxicol;5(6):505-12
Chinoy NJ, Narayana MV (1994). In vitro fluoride toxicity in human spermatozoa. Reprod Toxicol, Mar-Apr;8(2):155-9
Cohn PD (1992). An Epidemiologic Report on Drinking Water and Fluoridation. New Jersey Department of Health, Trenton, NJ.
Colquhoun J (1997). Why I changed my mind on Fluoridation. Perspectives in Biology and Medicine, 41, 29-44. http://www.fluoride-journal.com/98-31-2/312103.htm
Colquhoun, J. (1987). Studies of Child Dental Health Differences in New Zealand. Community Health Studies. 6(3): 85-90.
Connett P and Connett M. (2000). The emperor has no clothes: a critique of the CDC’s promotion of fluoridation. Waste Not # 468. 82 Judson Street, Canton NY 13617. http://www.fluoridealert.org/cdc.htm
DHHS (1991). Review of fluoride: benefits and risks, Report of the Ad Hoc Committee on Fluoride of the Committee to Coordinate Environmental Health and Related Programs. Department of Health and Human Services, USA.
DHHS (1993). Fluoridation Census 1992. Published by the U.S. Department of Health & Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Prevention Services, Division of Oral Health, Atlanta, Georgia 30333.
DenBesten P (1999). Biological mechanism of dental fluorosis relevant to the use of fluoride supplements. Community Dent. Oral Epidemiol., 27, 41-7.
Diesendorf M (1986). The mystery of declining tooth decay. Nature, 322, 125-129. http://www.fluoridealert.org/diesendorf.htm
Emsley J et al. (1981). An unexpectedly strong hydrogen bond: ab initio calculations and spectroscopic studies of amide-fluoride systems. Journal of the American Chemical Society, 103, 24-28.
Filley CM (1998). The behavioural neurology of cerebral white matter. Neurology; 50:1535-1540. (Cited by Filley, 2001).
Filley CM (2001). The behavioral neurology of white matter. New York: Oxford University Press.
Flechsig P (1901). Developmental (myelogenetic) localisation of the cerebral cortex in the human subject. Lancet; 2:1027-1029. (Cited by Filley, 2001).
Fletcher JM et al. (1992). Cerebral white matter and cognition in hydrocephalic children. Arch Neurol; 49:818-824. (Cited by Filley, 2001).
Galletti P and Joyet G (1958). Effect of fluorine on thyroidal iodine metabolism in hyperthyroidism. Journal of Clinical Endocrinology; 18:1102-1110 http://www.fluoridealert.org/galletti.htm
Gutteridge DH et al. (2002). A randomized trial of sodium fluoride (60 mg) Estrogen in Postmenopausal Osteoporotic Vertebral Fractures: Increased Vertebral Fractures and Peripheral Bone Loss with Sodium Fluoride; Concurrent Estrogen Prevents Peripheral Loss, But Not Vertebral Fractures. Osteoporosis International. Vol. 13 No. 2: 158-170.
Hedlund LR, Gallagher JC (1989). Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride. J Bone Miner Res Apr;4(2):223-5.
Heller KE et al. (1997). Dental caries and dental fluorosis at varying water fluoride concentrations. J of Pub Health Dent, 57;No. 3, 136-143.
Hirzy JW (1999). Why the EPA’s headquarters union of scientists opposes fluoridation. Press release from National Treasury Employees Union, May 1, 1999. (for text see http://www.fluoridealert.org/hp-epa.htm )
IOM (Institute of Medicine) (1997). Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board. National Academy Press.
Kandel et al. (2000). Principles of neural science. 4th ed. New York: McGraw-Hill. (Cited by Filley, 2001).
Klingberg T et al. (1999). Myelination and organization of the frontal white matter in children: a diffusion tensor MRI study. Neuroreport; 10:2817-2821. (Cited by Filley, 2001).
Kumar A, Susheela AK (1994). Ultrastructural studies of spermiogenesis in rabbit exposed to chronic fluoride toxicity.
Int J Fertil Menopausal Stud, May-Jun;39(3):164-71
Lalumandier JA et al. (1995). The prevalence and risk factors of fluorosis among patients in a pediatric dental practice. Pediatric Dentistry – 17:1, 19-25.
Li Y, C Liang et al. (1999). Effect of long-term exposure to fluoride in drinking water on risks of bone fractures. J Bone Miner Res.16(5):932-9.
Lin FF et al. (1991). The relationship of a low-iodine and high-fluoride environment to subclinical cretinism in Xinjiang. Iodine Deficiency Disorder Newsletter 7.
Locker D (1999). Benefits and risks of water fluoridation. An update of the 1996 federal-provincial sub-committee report. Prepared for Ontario Ministry of Health and Long Term Care.
Lu Y et al. (2000). Effect of high-fluoride water on intelligence of children. Fluoride, 33, 74-78.
Luke J (1997). The effect of fluoride on the physiology of the pineal gland. Ph.D. Thesis. University of Surrey, Guilford.
Luke J (2001). Fluoride deposition in the aged human pineal gland. Caries Res. 35:125-128.
Marcus W (1990). Memorandum from Dr. William Marcus to Alan B. Hais, Acting Director Criteria & Standards Division ODW, US EPA, DATED MAY 1, 1990, and subsequent memos. These can be viewed on the web at http://www.fluoridealert.org/marcus.htm
Michael M, Barot VV, Chinoy NJ (1996). Investigations of soft tissue functions in fluorotic individuals of North Gujarat. Fluoride; 29:2;63-71.
Morgan L et al. (1998). Investigation of the possible associations between fluorosis, fluoride exposure, and childhood behavior problems. Pediatric Dentistry – 20:4, 244-252.
Mullenix PJ et al. (1995). Neurotoxiicty of sodium fluoride in rats. Neurotoxicology and Teratology.17:2, 169-177.
National Academy of Sciences (1977). Drinking water and health. National Academy Press, Washington, DC., pp. 388-389.
National Research Council (1993). Health effects of ingested fluoride. National Academy Press, Washington DC. Page 49.
NTP (National Toxicology Program) (1990). Toxicology and carcinogenesis studies of sodium fluoride in F344/N rats and B6C3f1 mice. Technical report Series No. 393. NIH Publ. No 91-2848. National Institute of Environmental Health Sciences, Research Triangle Park, N.C. The results of this study are summarized in the Department of Health and Human Services report (DHHS,1991).
Nolte J (1999). The human brain. 4th ed. St. Louis: Mosby. (Cited by Filley, 2001).
Schlesinger ER et al. (1956). Newburgh-Kingston caries-fluorine study XIII. Pediatric findings after ten years. Journal of the American Dental Association, 52
Strunecka A and Patocka J (1999). Pharmacological and toxicological effects of aluminofluoride complexes. Fluoride, 32, 230-242.
Susheela AK, Jethanandani P (1996). Circulating testosterone levels in skeletal fluorosis patients. J Toxicol Clin Toxicol, 34(2):183-9
Sutton P (1959). Fluoridation: errors and omissions in experimental trials. Melbourne University Press. First Edition.
Sutton P (1960). Fluoridation: errors and omissions in experimental trials. Melbourne University Press. Second Edition.
Sutton P (1996). The Greatest Fraud: Fluoridation. Lorne, Australia: Kurunda Pty. Ltd.
van der Knaap et al. (1991). Myelination as an expression of the functional maturity of the brain. Dev Med Child Neurol; 33:849-857. (Cited by Filley, 2001).
Varner JA et al. (1998). Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity. Brain Research, 784, 284-298.
Williams JE et al. (1990). Community Water Fluoride Levels, Preschool Dietary Patterns, and The Occurrence of Fluoride Enamel Opacities. J of Pub Health Dent; 50:276-81.
WHO (Online). WHO Oral Health Country/Area Profile Programme. Department of Noncommunicable Diseases Surveillance/Oral Health. WHO Collaborating Centre, Malmö University, Sweden. http://www.whocollab.od.mah.se/euro.html
Yakovlev PI, Lecours AR (1967). The myelogenetic cycles of regional maturation of the brain. In: Minkowki A, ed. Regional development of the brain in early life. Oxford: Blackwell Scientific Publications, 3-79. (Cited by Filley, 2001).
Yiamouyiannis JA (1990). Water fluoridation and tooth decay: Results from the 1986-87 national survey of U.S. schoolchildren. Fluoride, 23, 55-67. http://www.fluoridealert.org/DMFTs.htm
York Review. McDonagh M et al. (2000). A systematic review of public water fluoridation. NHS Center for Reviews and Dissemination, University of York, September 2000. A summary of the Review appeared in the British Medical Journal.
Zhao LB et al. (1996). Effect of high-fluoride water supply on children’s intelligence. Fluoride, 29, 190-192.
Zhao W (1998). Long-term effects of various iodine and fluorine doses on the thyroid and fluorosis in mice. Endocr Regul 32(2):63-70.
|Tolerances Requested by Dow:
In or On Raw Commodity
|Tolerances Requested by Dow:
On the Processed Products
|Almond||10||0.2||Corn, field, flour||26||0.01|
|Barley, grain||10||0.01||Corn, field, grits||10||0.01|
|Beechnut||30||6||Corn, field, meal||28||0.01|
|Brazil (nut)||30||6||Corn, field, oil *||3||?|
|Butternut||30||6||Corn, field, refined oil||3||9|
|Corn, field, grain||7||0.04||Rice, polished rice||18||0.01|
|Corn, pop, grain||7||0.04||Wheat, bran||40||0.01|
|Filbert||30||6||Wheat milled by products||35||0.01|
|Fruit, dried||5||0.05||Wheat, shorts||38||0.01|
|Rice, wild, grain||25||0.05|
See Tables at (scroll down) http://18.104.22.168/pesticides/Sulfuryl.F.Mar.2002comments.htm