Environmental exposure to fluoride compounds may occur as a result of natural processes (eg, volcanic emission) or contamination of rocks, soil, and water; or from industrial waste. Fluoride compounds (eg, sodium fluoride, sodium fluorosilicate, fluorosilicic acid) are added to human drinking water at a concentrations of ~1 mg/L in an effort to reduce dental caries. This recommendation is not universally accepted. Both acute and chronic toxicoses may result from ingestion of fluorides. Maximum tolerated concentrations of fluoride in animal feeds range from ~20–50 mg/kg (dry weight) in most species. In poultry, up to 200 mg/kg may be tolerated. However, these reported concentrations may vary depending on age, duration of exposure, nutritional and health status of individual animals. Animals with a relatively long production life span, such as dairy cattle, are reported to be more susceptible to fluorosis. Guidelines for appropriate concentrations of fluoride in drinking water provided to food producing animals are ~1–2 ppm.
Etiology and Pathogenesis of Fluoride Poisoning in Animals
Fluoride compounds are found naturally in rock phosphates and limestone. Waste from production of fertilizers and mineral supplements and metal ores resulting from steel and aluminum processing are frequent industrial sources of fluoride toxicosis. Fluoride dusts dispersed downwind from manufacturing facilities may contaminate forage crops for miles. When crops grown on contaminated soil contain increased concentrations of fluoride, this is due to physical contamination with soil particulates; there is minimal direct uptake of fluoride by plants.
Because of potential fluoride contamination of a variety of feed and water sources, it is recommended that feed-grade phosphates contain <1% fluoride. Acute exposure to high fluoride concentrations will cause corrosive damage to tissues. In contrast, chronic exposure, which is seen more frequently, causes delayed or impaired mineralization of bones and teeth. The solubility of fluoride compound to which the animal is exposed correlates with the extent of severity of toxicosis.
Soluble fluoride compounds; ~50% is excreted via the kidneys by means of glomerular filtration. Over 95% of the fluoride that is retained is deposited in the bones and teeth, forming hydroxyapatite after the interference with calcium metabolism and replacement of hydroxyl ions. When fluoride exposure occurs at low concentrations, the solubility of the teeth enamel is decreased, resulting in protection. At higher levels of exposure, the enamel becomes dense and brittle. If exposure occurs during pregnancy, developing bones and teeth are severely affected. Faulty, irregular mineralization of the matrix of bones and teeth associated with altered ameloblastic, odontoblastic, or osteoblastic activity ultimately results in poor enamel formation, exostosis, sclerosis, and osteoporosis.
Clinical Findings for Fluoride Poisoning in Animals
Generally, acute fluoride poisoning (fluorosis); for example, associated with massive ingestion of ascaricides (sodium fluoride), rodenticides (sodium fluorosilicate), or dental products for human oral use will produce clinical signs of disease within 2 hours. The fatal dosage of sodium fluoride is ~5–10 mg/kg in most commonly treated animal species. Signs of toxicosis may be evident after oral ingestion fluoride compounds at a concentration of ~1 mg/kg. Serum calcium and magnesium concentrations decrease rapidly after the onset of clinical signs.
Severe gastroenteritis, salivation, signs of restlessness, sweating, anorexia, muscle weakness, stiffness, dyspnea, ventricular tachycardia, and clonic convulsions; followed by depression and death are typically seen. Chronic fluorosis is characterized by signs of malnutrition and skeletal and dental abnormalities. Decreased feed and water intake accompanied by weight loss and poor milk production (eg in dairy cows) reflect dental lesions and impaired mastication. Mottled, chalky, pitted and stained enamel and uneven and excessive wear on the teeth are frequently seen. Dental pain manifested by lapping of drinking water may be apparent.
Skeletal abnormalities associated with increased bony resorption and remodeling produces severe lameness, stiffness, abnormal hoof growth, and exostoses. In later stages of the chronic fluorosis in cattle, severely affected animals may be forced to move on their knees due to extreme joint involvement. Periosteal hyperostosis frequently affects the ribs. Metabolically active, growing bones of young animals are more severely affected. Anemia and hypothyroidism manifested by reduced T3 and T4 and serum calcium concentrations are often evident.
On gross and histopathologic examination, severe gastrointestinal inflammation and degenerative changes in organs such as the liver, kidney, and lungs reflect the cytotoxic effects of acute fluorosis. After chronic exposure during pregnancy, fetuses and neonates are more severely affected. Bilateral and symmetrical skeletal abnormalities are present. The bones are chalky white with pathologic evidence of disrupted osteogenesis, accelerated bone remodeling, and resorption. Production of abnormal bone results in exostoses (most evident in long bones), sclerosis, and osteoporosis. The mandible, ribs, metacarpi, and metatarsi are most often affected. Teeth are mottled, chalky, stained and exhibit uneven wear; eruption of permanent incisor teeth may be delayed.
Diagnosis of Fluoride Poisoning in Animals
A history of exposure, environmental factors considered
Tentative diagnosis based on history, clinical evaluation and postmortem examination if fatal
Analysis of tissue, water and food samples to measure fluoride concentration provides valuable confirmatory evidence
A diagnosis of acute fluoride poisoning should be made on the basis of a history of exposure and typical clinical and histopathologic findings. Diagnostic confirmation with urine or serum testing should be interpreted with caution because rapid, time-dependent elimination of fluorides occurs. The measurement of serum calcium and magnesium concentrations may provide supportive evidence.
Chronic fluorosis may develop over many months. Detection of fluoride in tissues must be considered in association with history, clinical signs of disease, and, where relevant, necropsy findings. Animals exhibiting skeletal and dental abnormalities such as lameness, anorexia, productivity, and osteoporosis (eg, on diagnostic imaging) should be evaluated for chronic fluorosis.
Other disease syndromes such as arthritis; calcium, phosphorous, or vitamin D deficiency; metal toxicoses such as due to ingestion of molybdenum, selenium, or arsenic; and ergotism may be confused with chronic fluorosis. When evaluating animals, radiography and histologic evaluation of tissue specimens, with serum testing, may prove useful.
In food-producing animals, normal fluoride concentrations in the diet range from ~20–50 mg/kg. Depending on the duration of exposure and species susceptibility, concentrations in the diet ranging from 100–300 mg/kg may produce chronic poisoning. Water concentrations >30 mg/L are considered toxic. In young dairy cattle with a lengthy lifetime production potential, tolerance levels should be reduced by at least twofold. Because fluoride does not accumulate in soft tissue, analysis of liver and kidney has limited usefulness.
In food producing animals, reference range for plasma fluoride concentration is <0.2 mg/L, whereas concentrations ranging from 0.7 to 1.9 mg/L are consistent with fluorosis. Corresponding urinary concentrations <0.5 mg/L are considered normal. Toxic concentrations suggestive of recent exposure range from 14–120 mg/L. Fluoride concentrations detected in bones and teeth may reach concentrations as high as 1,500 mg/kg and 1,000 mg/kg, respectively, without apparent adverse effects. Concentrations ranging from 6,000 to 13,000 mg/kg and 7,500 to 11,000 mg/kg, respectively, are consistent with a diagnosis of chronic fluorosis in food producing animals. Plasma concentrations may increase substantially once the skeletal concentrations of fluoride approach saturation.
Treatment and Control of Fluoride Poisoning in Animals
Treatment objectives are to eliminate absorption of fluoride compounds and maintain adequate fluid status in animals with signs of acute fluorosis. The prognosis and treatment response in chronic cases is poor because permanent damage has occurred.
Animals developing acute toxicosis may be administered calcium gluconate (IV) and magnesium hydroxide or milk by orally to minimize fluoride absorption, although the prognosis may be poor if massive amounts of fluoride were ingested. Once manifestations of chronic fluorosis develop, treatment is ineffective. The primary objective should be directed toward prevention. In many instances, it may be difficult or impractical to remove food producing animals from contaminated areas. Supplementation with calcium carbonate, aluminum salts, magnesium metasilicate, or boron will reduce absorption or enhance excretion. It is recommended that food producing animals consume supplements and mineral mixes containing <1% fluoride content. If it is impractical to limit fluoride exposure, raising species with a relatively short production life, such as poultry, pigs, or sheep, should be considered. Reducing fluoride exposure of young or pregnant animals may limit the development of chronic fluorosis. Animals with goiter, renal disease, and diabetes insipidus may also be at greater risk. If it is practical, filtered or bottled water may reduce exposure via drinking water.
The benefits of fluoride supplementation balanced with the potential of adverse effects including permanent developmental disease and a lack of an effective treatment for fluoride toxicosis deserve careful consideration.