Fluorosis occurs after excessive fluoride intake and can be acute or chronic. Acute fluorosis is uncommon and is characterized by GI irritation and cardiovascular abnormalities, whereas chronic fluoride exposure results in excessive wear of teeth, lameness, and exostosis in bone. Fluoride toxicosis can be confirmed by analyzing urine or serum for acute exposures, bone for chronic exposures, and source material (feed, water, etc) for both. No specific antidote exists for fluoride toxicosis. Acute cases demand supportive care and correction of clinical signs, whereas chronic cases do not respond favorably to treatment. Preventing excessive exposure is essential.
Animal exposure to fluoride compounds can occur as a result of natural processes (eg, volcanic emissions contaminating forages), contamination of feed and water by industrial waste, or accidental exposure to fluoride-containing compounds meant for human oral care (toothpaste, etc). Feed-grade phosphate sources are often obtained from fluorine-containing phosphate rock. These sources are defluorinated to meet standards designed to control dietary fluoride in livestock diets. However, residual fluoride can remain, depending on the source material and processing efficiency (1, 2).
Fluoride compounds (eg, fluorosilicic acid, sodium fluorosilicate, and sodium fluoride) are added to human drinking water at a concentration of 0.7 mg/L in an effort to decrease dental caries in the US (3). This recommendation is not universally accepted. Both acute and chronic toxicoses can result from ingestion of fluoride compounds. Because some animals are managed on the same water source as humans, the addition of fluoride could be relevant in an investigation of fluoride poisoning in animals.
Maximum tolerated concentrations of fluoride in animal feeds for different species are listed in the table (4). However, these reported concentrations can vary depending on age, duration of exposure, and nutritional and health status of individual animals. Young animals and those with a relatively long production lifespan are reported to be more susceptible to fluorosis.
Long-Term Maximum Tolerable Dietary Levels of Fluoridesa
Animals | Maximum Tolerable Dietary Levels of Fluorides |
|---|---|
Dairy replacement calves and bull calves intended for breeding | 30–40 mg F/kg dry matter |
Beef calves | 40 mg F/kg dry matter |
Adult dairy cattle | 40 mg F/kg dry matter |
Adult beef cattle | 50 mg F/kg dry matter |
Fattening cattle | 100 mg F/kg dry matter |
Breeding ewes | 60 mg F/kg dry matter |
Fattening lambs | 150 mg F/kg dry matter |
Horses | 40 mg F/kg dry matter |
Rabbits | 40 mg F/kg dry matter |
Pigs | 150 mg F/kg dry matter |
Turkeys | 150 mg F/kg dry matter |
Chickens | 200 mg F/kg dry matter |
Abbreviations: F, fluoride. | |
Adapted from Mineral Tolerance of Animals. 2nd rev ed. National Academy of Sciences. National Academies Press. 2005:154-181. | |
aThis table assumes high-availability sources, such as sodium fluoride, and that drinking water contains less than 3 mg F/L. | |
Drinking water provided to food-producing animals should contain less than 2 mg/L of total fluoride; this threshold is dependent on the dietary inclusion, because feed and water fluoride sources are additive (4).
Pearls & Pitfalls
|
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 can contaminate forage crops for miles. When crops and forages are grown on fluoride-contaminated soil, some fluoride can be absorbed by the plants; however, the most important contamination occurs from particulates settling on plant surfaces (5). Some ground water sources have been implicated in chronic poisonings (6).
Because of potential fluoride contamination of a variety of feed and water sources, feed-grade phosphates are recommended to contain < 1% fluoride. Acute exposure to high fluoride concentrations will cause corrosive damage to tissues of the GI tract and rapidly chelate calcium and magnesium, resulting in the cardiovascular signs appreciated in these cases. In contrast, the more frequent chronic exposure scenario causes delayed or impaired mineralization of bones and teeth. The solubility of the fluoride compound to which the animal is exposed correlates with the extent of absorption and the severity of toxicosis.
For soluble fluoride compounds, approximately half of absorbed fluoride is excreted via the kidneys by means of glomerular filtration. Most of the retained fluoride 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 tooth 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 produces clinical signs of disease within 2 hours. Serum calcium and magnesium concentrations decrease rapidly after the onset of clinical signs. Severe gastroenteritis, salivation, restlessness, sweating, anorexia, muscle weakness, stiffness, dyspnea, ventricular tachycardia, and clonic convulsions, followed by depression and death, can occur. Acute lethal doses historically reported in veterinary texts (5–10 mg/kg body weight [BW]) likely underestimate the true LD50 derived from controlled rodent studies (> 40 mg/kg BW) (7). Severe clinical signs can occur at lower doses because of a variety of animal factors, including individual susceptibility and comorbidities that might have contributed to lower historical estimates.
Chronic fluorosis is characterized by malnutrition with prominent dental and skeletal abnormalities. Decreased feed and water intake, weight loss, and decreased milk production in lactating animals result from dental lesions that impair mastication. Teeth are often mottled, chalky, and pitted, with stained enamel, and wear unevenly and rapidly. Dental pain may be evident, and animals may lap water or drink abnormally. Skeletal lesions result from increased bone resorption and remodeling and cause lameness, stiffness, and reluctance to move. Bony exostoses around joints can limit range of motion and force animals to move on their carpal joints. Periosteal hyperostosis commonly affects the ribs and mandible, and the metabolically active bones of younger animals are more severely affected.
Lesions
Acute fluorosis is associated with severe GI inflammation and degenerative changes in the liver, kidney, and lungs from the direct cytotoxicity of fluoride. The direct cytotoxicity of fluoride is partially mediated by mitochondrial dysfunction and oxidative stress (8). Chronic exposure causes skeletal changes that are more severe in fetuses and young animals if their dam was exposed during pregnancy. The skeletal changes are often bilateral and symmetrical. Abnormal bone formation leads to exostoses, sclerosis, and osteoporosis of the ribs, mandible, metacarpi, and metatarsi. Dental lesions include mottled or stained enamel with uneven wear; delayed eruption of permanent incisors can occur.
Diagnosis of Fluoride Poisoning in Animals
History of potential fluoride exposure including environmental, feed, and water sources
Clinical and postmortem findings
Fluoride analysis of serum, urine, and bone, as well as feed and water, to confirm and estimate exposure
Diagnosis is based on a history of exposure, environmental assessment, and clinical findings, with postmortem examination when applicable. Measurement of fluoride concentrations in feed, water, and tissues provides confirmatory evidence. Acute fluorosis is diagnosed primarily via exposure history and characteristic clinical and histopathological findings. Serum or urine fluoride concentrations should be interpreted with caution because of the rapid elimination of fluoride. Serum calcium and magnesium concentrations can be supportive.
Pearls & Pitfalls
|
Chronic fluorosis develops over months and should be considered in animals with lameness, anorexia, decreased productivity, dental abnormalities, or radiographic confirmation of osteoporosis. Radiographic evaluation and histological examination of tissues, combined with serum, urine, and bone fluoride concentrations, can aid in diagnosis. Importantly, not all diagnostic laboratories offer this analysis, so veterinarians are encouraged to communicate with their laboratory of choice to determine testing capacity.
Antemortem diagnosis of fluoride toxicosis relies heavily on dental lesions, documented skeletal lesions, and elevated urine or plasma fluoride concentrations. Elevated urine fluoride concentrations (15–20 ppm, compared to 2–6 ppm normally) could be due to either recent exposure or continued elimination from bone (9). Normal plasma concentrations may be species-specific; eg, concentrations > 0.7 ppm are considered toxic in cattle (10).
Bone biopsies, while potentially cost- and labor-prohibitive in many food-producing animals, can be used for diagnostic purposes. Cancellous bone contains more fluoride than cortical bone with normal fluoride concentrations from 400 to 1200 ppm (dry, defatted basis). Bone from clinical fluoride cases often exceeds 3,000 ppm, with bone ash concentrations approximately one-third higher (9). Bones selected for diagnosis include ribs or coccygeal vertebrae.
Feed and water evaluation should also be performed to estimate total dietary intake. Water concentrations > 30 ppm are considered toxic (10).
Treatment and Control of Fluoride Poisoning in Animals
No specific antidote for acute or chronic toxicosis
Largely supportive treatment of clinical cases
Salvage or euthanasia in severe cases
Controlling exposure to excessive fluoride is the most important tenet of control. Modern dietary supplements for veterinary species are generally of high quality with low fluoride concentrations, and clinical cases of fluorosis are rare. Adequate dietary supplementation of other minerals and limited grazing of contaminated areas can help lower the fluoride burden. Consideration of all dietary components, including water, is necessary to determine the major contributors of fluoride to the diet of animals with clinical disease.
Key Points
Fluorosis in animals is most often a chronic disease rather than an acute toxicosis. The exposure is typically related to the environment and animal management in the production system.
Diagnosis depends on exposure history and appropriate sample selection; blood testing alone is insufficient.
No effective treatment exists for chronic fluorosis. Prevention by controlling exposure is critical.
For More Information
Shupe JL. Clinicopathologic features of fluoride toxicosis in cattle. J Anim Sci. 1980;51(3):746-758.
Shupe JL, Olson AE. Clinical aspects of fluorosis in horses. J Am Vet Med Assoc. 1971;158(2):167-174.
Kessabi M, Hamliri A, Braun JP, Rico AG. Experimental acute sodium fluoride poisoning in sheep: renal, hepatic, and metabolic effects. Fundam Appl Toxicol. 1985;5(6 Pt 1):1025-1033.
References
Joshi AN. A review of processes for separation and utilization of fluorine from phosphoric acid and phosphate fertilizers. Chem Pap. 2022;76(144):6033-6045. doi:10.1007/s11696-022-02323-9
Thompson DJ. Industrial considerations related to fluoride toxicity, J Anim Sci. 1980;51(3):767-772, doi:10.2527/jas1980.513767x
US Dept of Health and Human Services Federal Panel on Community Water Fluoridation. US Public Health Service Recommendation for Fluoride Concentration in Drinking Water for the Prevention of Dental Caries. Public Health Rep. 2015;130(4):318-331. doi:10.1177/003335491513000408
National Research Council Committee on Minerals and Toxic Substances in Diets and Water for Animals. Fluorine. In: Mineral Tolerance of Animals. 2nd rev ed. National Academies Press; 2005:154-181. doi:10.17226/11309
Livesey C, Payne J. Diagnosis and investigation of fluorosis in livestock and horses. In Pract. 2011;33:454-461. doi:10.1136/inp.d6078
Kelly LH, Uzal FA, Poppenga RH, et al. Equine dental and skeletal fluorosis induced by well water consumption. J Vet Diagn Invest. 2020;32(6):942-947. doi:10.1177/1040638720962746
Leone NC, Geever EF, Moran NC. Acute and subacute toxicity studies of sodium fluoride in animals. Public Health Rep (1896). 1956;71(5):459-467.
Wei M, Ye Y, Ali MM, Chamba Y, Tang J, Shang P. Effect of fluoride on cytotoxicity involved in mitochondrial dysfunction: a review of mechanism. Front Vet Sci. 2022;9:850771. doi:10.3389/fvets.2022.850771
Osweiler G. Fluoride. In: Plumlee KH, ed. Clinical Veterinary Toxicology. Mosby; 2004:197-200.
Puls R. Mineral Levels in Animal Health: Diagnostic Data. 2nd ed. Sherpa International; 1994:82.
