Sulfuryl Fluoride; Proposed Pesticide Temporary Tolerances. Federal Register: September 5, 2001 (Volume 66, Number 172)] [Proposed Rules] [Page 46415-46425]. ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 180 [OPP-301166; FRL-6799-6] RIN 2070-AC18. http://www.fluoridealert.org/pesticides/Sulfuryl.Flu.FR.Sept.5.2001.htm

-- In 2-week inhalation studies in rats, dogs and rabbits, different target organs were affected... 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, histopathology in the lungs, and follicular cell hypertrophy in the thyroid gland were observed.

-- In a 2-generation reproduction inhalation study in rats, vacuolation of the white matter in the brain...

Neurotoxicol Teratol 1998 Sep-Oct;20(5):537-42
Influence of chronic fluorosis on membrane lipids in rat brain.
Guan ZZ, Wang YN, Xiao KQ, Dai DY, Chen YH, Liu JL, Sindelar P, Dallner G.
PMID: 9761592 [PubMed - indexed for MEDLINE]

Brain membrane lipid in rats were analyzed after being fed either 30 or 100 ppm fluoride for 3, 5, and 7 months. The protein content of brain with fluorosis decreased, whereas the DNA content remained stable during the entire period of investigation. After 7 months of fluoride treatment, the total brain phospholipid content decreased by 10% and 20% in the 30 and 100 ppm fluoride groups, respectively. The main species of phospholipid influenced by fluorosis were phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine. The fatty acid and aldehyde compositions of individual phospholipid classes were unchanged. No modifications could be detected in the amounts of cholesterol and dolichol. After 3 months of fluoride treatment, ubiquinone contents in brain were lower; however, at 7 months they were obviously increased in both groups of fluoride treatment. The results demonstrate that the contents of phospholipid and ubiquinone are modified in brains affected by chronic fluorosis and these changes of membrane lipids could be involved in the pathogenesis of this disease.

Some excerpts from: 2002 - FLUORIDES. Environmental Health Criteria 227. World Health Organization, Geneva. This 224 page report was released on August 8, 2002.

The use of fluoride-containing pesticides as well as the fluoridation of drinking-water supplies also contribute to the release of fluoride from anthro-pogenic sources...

The relative contribution of various anthropogenic sources to total emissions of fluoride to air, water and soil in Canada are estimated at 48% for phosphate fertilizer production, 20% for chemical production, 19% for aluminium production, 8% for steel and oil production and 5% for coal burning

The concentration of fluoride in food products is not signifi-cantly increased by the addition of superphosphate fertilizers, which contain significant concentrations of fluoride (1Ð3%) as impurities, to agricultural soil, due to the generally low transfer coefficient from soil to plant material. However, a recent study suggests that, given the right soil conditions and application of sufficient fluoride as an impurity in phosphate fertilizers to soils, plant uptake of fluoride can be increased. The use of water containing relatively low (<3.1 mg/litre) levels of fluoride for crop irrigation generally does not increase fluoride concentrations in foodstuffs. However, this is dependent on plant species and fluoride concentrations in soil and water. The level of fluoride in foods is significantly affected by the fluoride content of the water used in preparation or processing, most notably in beverages and dry foodstuffs Ñ for example, powdered baby formula Ñ to which water is added prior to consumption. The concentrations of fluoride in unwashed or unprocessed foods grown in the vicinity of industrial sources (emissions) of fluoride may be greater than the levels in the same foods grown in other non-industrially exposed areas. In commer-cially available infant formulas sold in the USA, soy-based ready-to-use and liquid concentrate formulas contained higher levels of fluoride than the equivalent milk-based products; however, no significant difference was observed between soy- and milk-based powdered infant formulas.

Aluminium smelters, brickworks, phosphorus plants and fertilizer and fibreglass plants have all been shown to be sources of fluoride that are correlated with damage to local plant communities. Vegetation in the vicinity of a phosphorus plant revealed that the degree of damage and fluoride levels in soil humus were inversely related to the distance from the plant. Average levels of fluoride in vegetation ranged from 281 mg/kg in severely damaged areas to 44 mg/kg in lightly damaged areas; at a control site, the fluoride concentration was 7 mg/kg. Plant communities near an aluminium smelter showed dif-ferences in community composition and structure due partly to varia-tions in fluoride tolerance. However, it must be noted that, in the field, one of the main problems with the identification of fluoride effects is the presence of confounding variables such as other atmospheric pollutants. Therefore, care must be taken when interpreting the many field studies on fluoride pollution. (page 13)

... there is a potential risk from fluoride-contaminated pasture and soil ingestion due to the long-term use of phosphate fertilizers containing fluoride as an impurity.

Phosphate fertilizers Phosphate fertilizers are the major source of fluoride contami-nation of agricultural soils. They are manufactured from rock phos-phates, which generally contain around 3.5% fluorine (Hart et al., 1934). However, during the manufacture of phosphate fertilizers, part of the fluoride is lost into the atmosphere during the acidulation process, and the concentration of fluoride in the final fertilizer is lowered further through dilution with sulfur (superphospha tes) or ammonium ion (ammoniated phosphates); the final product commonly contains between 1.3 and 3.0% fluorine (McLaughlin et al., 1996). In Australia, an average annual addition of fluoride to soil through fertilization has been estimated to be 1.1 kg/ha. (pages 22-23)

Terrestrial plants may accumulate inorganic fluorides following airborne deposition and uptake from the soil (Davison, 1983). Sloof et al. (1989) reported that the main route of uptake of fluoride by plants is from aerial deposition on the plant surface. Plant uptake from soil is generally low (except for accumulators) unless the fluoride has been added suddenly, such as following amendment with sludge or phos-phate fertilizer. The availability to plants tends to decrease with time following application of fluoride. The degree of accumulation depends on several factors, including soil type and, most prominently, pH. At acidic pH (below pH 5.5), fluoride becomes more phytoavailable through complexation with soluble aluminium fluoride species, which are themselves taken up by plants or increase the potential for the fluoride ion to be taken up by the plant (Stevens et al., 1997). Plant uptake of fluoride from solution culture is dependent on plant species and positively related to the ionic strength of the growth solution. Once a threshold fluoride ion activity in nutrient solutions is reached, fluoride concentrations in plants increase rapidly (Stevens et al., 1998a). (Page 35-36)

The concentration of fluoride in food products is usually not significantly increased by the addition of superphosphate fertilizers to agricultural soil (Oelschlþger, 1971), due to the generally low transfer coefficient from soil to plant material. However, a recent study by McLaughlin et al. (2001) found significant increases in fluoride concentrations in herbage harvested from plots fertilized with phosphate fertilizers (537 kg total phosphorus added over 59 years) over a long period (22 mg fluoride/kg) compared with concentrations in herbage harvested from unfertilized plots (11 mg fluoride/kg). These data suggest that, given the right soil conditions and application of sufficient fluoride as an impurity in phosphate fertilizers to soils, plant uptake of fluoride can be increased. The use of water containing rela-tively low (<3.1 mg/litre) levels of fluoride for crop irrigation generally does not increase foodstuff fluoride concentrations (Schamschula et al., 1988a). However, this is dependent on plant species and fluoride concentrations in soil and water. For example, Kabasakalis & Tsolaki (1994) showed that fluoride concentrations in vegetables irrigated with water containing 10 mg fluoride/litre were increased compared with fluoride concentrations in vegetables grown with irrigation water con-taining low fluoride concentrations (0.15 mg/litre). They also commented that fluoride has a tendency to accumulate in the vegetable leaves rather than in the fruits.

Levels of fluoride in foods are significantly affected by the fluoride content of the water used in preparation or processing, most notably in beverages and dry foodstuffs to which water is added prior to consumption (Kumpulainen & Koivistoinen, 1977; Schamschula et al., 1988a). In a study conducted in a rural area of China, immersion of vegetables in hot spring water containing elevated levels of fluoride (approximately 20.3 mg/litre) reportedly led to a significant increase in the fluoride content of the food product (Xu et al., 1995). The concentration of fluoride in water used to parboil rice influenced the level in the final product (Anasuya & Paranjape, 1996). The concentrations of fluoride in unwashed or unprocessed foods grown in the vicinity of industrial sources (emissions) of fluoride in Japan (Sakurai et al., 1983; Tsunoda & Tsunoda, 1986; Muramoto et al., 1991) and the United Kingdom (Jones et al., 1971) have been up to 100-fold greater than the levels in the same foods grown in other non-industrially exposed areas.

Genotoxic effects. The mean frequency of sister chromatid exchange in peripheral blood lymphocytes obtained from 40 Chinese fertilizer production workers was significantly (P < 0.01) increased by approximately 50%, compared with that in a similarly sized group of controls matched for age, sex and smoking habits (Meng et al., 1995). During the period of analysis, workers were exposed to levels of fluoride (mostly hydro-fluoric acid and silicon tetrafluoride) ranging from 0.5 to 0.8 mg/m 3 , as well as to phosphate fog, ammonia and sulfur dioxide. Among the workers, the average frequency of sister chromatid exchange was approximately 27% higher (P < 0.01) in smokers than in non-smokers. Information on the total intake of fluoride was not presented. In a further study, an increased frequency of both chromosomal aberrations and micronuclei in circulating blood lymphocytes was also observed among the fertilizer plant workers (n = 40), in comparison with 40 controls working and studying in Shanxi University, situated in the same city as the factory, matched for sex, age and smoking habits (Meng & Zhang, 1997); the microscopic analysis was performed on coded slides. (page 128-129)

Two excerpts from: 2001 - Environment Canada. Canadian Water Quality Guidelines for the Protection of Aquatic Life: Inorganic Fluorides.

Inorganic fluorides act as enzyme inhibitors and have wide-ranging effects. Adverse effects observed in aquatic organisms include: changes in blood composition; reduced size and growth; slowed embryonic and developmental life stage; impaired reproduction; and abnormal or impaired behavior (e.g., fish migration). Inorganic fluorides are also neurotoxic, causing adverse effects on the central nervous system. Inorganic fluoride toxicity is negatively correlated with water hardness (calcium) and positively corelated with temperature...

Anthropogenic Sources. In Canada, the primary anthropogenic emission sources of inorganic fluorides are phosphate fertiliser production (34.6%), and aluminum smelting operations (35.2%). Other important emission sources include coal burning facilities, oil refining, steel production, chemical producers, primary copper and nickel production, clay production, magnesium smelting, lead and zinc smelting, glass and enamel making, brick and ceramic manufacturing, production of glues and adhesives, fluoridation of drinking water, fluoride-containing pesticides, waste from sewage sludge, and the production of uranium trifluoriide (UF3) and uranium hexafluoride (UF6) for the nuclear electric industry (page 9).

November 1978 Research Report 365: Fluorosis from phosphate mineral supplements in Michigan dairy cattle by Hillman D, Bolenbaugh D, Convey EM. Michigan State University Agricultural Experiment Station, East Lancing.

Excerpts from abstracted version published in Fluoride 1979; 12(2):100-102:
During 1975 and 1976 more than 75 Michigan dairymen reported in their cows subnormal milk production, loss of weight after calving, failure to exhibit estrus or to re-breed as expected as well as a high incidence uterine infections and lameness. Death from undetermined causes ranged between 10 and 15 percent among adult cows and among calves up to 1 year or more in age many failed to grow normally or died from undetermined causes. Analysis of milk and tissue fat for PBB (polybrominated biphenyls) which had been responsible for a similar epidemic in Michigan reealed no detectable traces. Severe dental fluorosis and exostoses of etatarsal bones led to the discovery that mineral suppements containing up to 6300 ppm of fluoride and protein supplements containing up to 1088 ppm fluoride consumed by the cows were responsible for this epidemic.

... The thyroids of calves were enlarged 2 to 5 times their normal weight and the cows afficted with fluorosis showed evidence of hypo-thryoidism. The depression of the serum thyroxine (T4) and triiodothyronine (T3) correlated with the increase in urinary fluoride, with the number of red blood cells, with the hemoglobin, serum cholesterol, calcium, glucose and albumin. Fluoride also decreased the serum cholesterol at a lower level of significance (P <.06).

With respect to the hematological findings eosinophilia increased in correlation with urinary fluoride (P <.004) and should be considered an early manifestation of fluoride toxicity. Moreover fluorotic animals manifested anemia...

The authors suggested that the National Research Council recommendation of a level of 30 ppm maximum dietary fluoride "may be too high for high producing dairy cattle fed phosphate sources of fluoride."