A Brief and Critical Review of Skeletal Fluorosis in Domestic Animals and its Adverse Economic Consequences
Shanti Lal Choubisa*
Department of Advanced Science and Technology, National Institute of Medical Science and Research, NIMS University Rajasthan, Jaipur, Rajasthan 303121, India; Former Department of Zoology, Government Meera Girls College, MLS University, Udaipur, Rajasthan 313001, India.
Submission:May 20, 2024;Published:May 27, 2024
*Corresponding author: Shanti Lal Choubisa, Department of Advanced Science and Technology, National Institute of Medical Science and Research, NIMS University Rajasthan, Jaipur, Rajasthan 303121, India; Former Department of Zoology, Government Meera Girls College, MLS University, Udaipur, Rajasthan 313001, India. E-mail: choubisasl@yahoo.com
How to cite this article: Choubisa SL. A Brief and Critical Review of Skeletal Fluorosis in Domestic Animals and its Adverse Economic Consequences. Dairy and Vet Sci J. 2024; 16(4): 555942.DOI: 10.19080/JDVS.2024.16.555942
Abstract
When herbivorous domestic animals, such as cattle (Bos taurus), water buffaloes (Bubals bubalis), sheep (Ovis aries), goats (Capra hircus), camels (Camelus dromedarius), horses (Equus caballus), and donkeys (E. asinus) are exposed to fluoride through fluoride- contaminated drinking water and food and air-borne fluoride over a long period of time, then fluorosis is developed in them. The disease generally manifests as dental fluorosis (dental deformities) and skeletal fluorosis (bone deformities). In fact, the latter is more dangerous and is a life-long, extremely painful, and incurable fluoride-induced bone disease and results from excessive accumulation of fluoride in various bones. In skeletal fluorosis, the bones of animals become weak, hard, and less flexible and at an early age of animals the mobility of the joints also decreases. The most common bone changes or pathologies such as periosteal exostosis, osteoporosis, osteoporosis, and osteophytosis are found in severe skeletal fluorosis and are clinically manifested as vague pain in the body and joints. Excessive accumulation of fluoride in muscles also reduces mobility and this condition leads to disability or lameness in animals. Globally, thousands of domestic animals suffer from skeletal fluorosis in fluoride endemic rural areas. However, the severity of bone deformities such as periosteal hyperostosis and osteophytosis increases with increasing bone fluoride levels. Typically, skeletal fluorosis develops or appears above a bone fluoride level of 2,500 ppm. The present communication briefly and critically reviews the various sources of fluoride exposure, the severity of fluoride-induced skeletal fluorosis in domestic animals and its adverse economic consequences, and the methods to prevent this dangerous bone disease. The findings of this review may contribute to the formulation and implementation of health plans for mitigation of skeletal fluorosis in domestic animals and are also useful for livestock farmers.
Keywords:Adverse economic consequences; Bone disease; Bone fluoride level; Domestic animals; Fluoride; Fluoride toxicity; Fluorosis; Lameness; Prevention; Skeletal fluorosis
Introduction
It is well known that fluorosis in animals results from long-term exposure to fluoride through fluoride-contaminated drinking water and food and airborne fluoride (industrial fluoride emissions). However, fluoridated water and industrial fluoride pollution are the main sources of development of fluorosis in animals. Fluorosis developed from these sources is called hydro fluorosis and industrial fluorosis in man and animals, respectively [1-8]. However, former disease is most common in domestic animals while foodborne fluorosis in animals is rare in occurrence. Fluorosis is not only prevalent in domestic [9-40] and wild [41-48] animals but it is also prevalent in human populations when exposed to fluoride for long-time [49-61]. In the world, India, and China, both countries are hyperendemic of fluorosis disease. However, fluorosis in diverse species of domestic animals, such as cattle (Bos taurus), water buffaloes (Bubals bubalis), sheep (Ovis aries), goats (Capra hircus), camels (Camelus dromedarius), horses (Equus caballus), and donkeys (E. asinus) has been well studied in relation to various fluoride levels in drinking waters, age, sex, different environments or ecosystems, and species [10, 17,18, 22-24, 26]. In fact, in India, almost all drinking water sources of domestic animals in rural areas are contaminated with fluoride with varying amounts [62-65].
In fluorosis, generally, teeth and bones are greatly affected with varying grades depending upon the concentration of fluoride and the duration of exposure. However, soft tissues or organs are also affected by fluoride toxicity. When teeth are affected by chronic fluoride toxicity it is known as dental fluorosis while when bones are deformed or affected it is known as skeletal fluorosis. The term non-skeletal fluorosis is also used when soft tissues or organs are affected by fluoride [1,66,67]. Dental and skeletal fluorosis are generally irreversible while non-skeletal fluorosis is reversible [66,67]. The present critical review focuses on how skeletal fluorosis develops and is dangerous to domestic animals and its impact on the economy of livestock keepers and how to prevent this bone disease in domesticated animals. The findings of this review may contribute to the formulation and implementation of health plans for mitigation of skeletal fluorosis in domestic animals and are also useful for livestock farmers.
Sources of Fluoride Exposures for Animals
Fluorine (F-) is the seventeenth most abundant substance in the Earth’s crust [1] and is widely distributed in sea water, fresh and ground waters, soil, dust, and mineral deposits. Major sources of fluoride exposure to domestic animals are fluoridated drinking water, vegetation and agricultural crops growing on fluoride contaminated soil and water, fluoridated phosphate feed supplements, mineral admixtures, dust in the air, and some industrial processes such as coal burning power generation stations, and manufacture of steel iron, aluminum, zinc, phosphorus, chemical fertilizers, bricks, glass, plastics, cement, hydrofluoric acid, etc. These industrial processes typically release fluoride into the surrounding environment in both gaseous and particulate/dust forms [1,4]. Eventually, the emitted industrial fluoride gets accumulated in soil and herbs/vegetation and contaminates fresh water sources, such as rivers, lakes, ponds, reservoirs, etc. However, the main source of fluoride exposure in domestic animals is drinking water. In fluorosis endemic India, fluoride levels above 3.0 and 21.0 ppm have been recorded in surface and ground water sources, respectively [6, 10]. In rural areas, fluoride contaminated groundwater is commonly used for irrigation in agriculture. This is why agricultural feed is also found to be contaminated with fluoride. Such feed is also a potential source of fluoride for domestic animals [68, 69].
Absorption, Excretion, and Accumulation of Fluoride
Soluble fluorides are almost completely absorbed from the gastrointestinal tract and are carried to various parts of the body via the blood circulation system [70,71], with maximum plasma levels attained within 20-60 minutes of oral intake [71, 72]. However, fluoride absorption may be reduced by the formation of insoluble complexes or precipitates with food components. Fluoride can cross biological membranes by diffusion as nonionic hydrogen fluoride (HF) [73]. Fluoride has also been reported to cross the placenta [74,75]. However, the greatest amount of absorbed fluoride is retained or accumulated in the growth or remodeling of calcified organs, such as bone and teeth [76], where approximately 99% of the total fluoride in an organism is found [77]. In contrast, fluoride concentrations may be higher in the kidney than in plasma [78]. Finally, most of the absorbed fluoride is excreted by the kidney, and only a small fraction via the feces [79]. In any case, fluoride concentrations in bones will increase as animals age, even in areas with low environmental fluoride [80]. Fluoride absorption by the skeleton is nearly 100% in growing animals, and the rate slows as bones mature [81].
Skeletal Fluorosis in Domestic Animals
Biological accumulation of fluoride causes diverse toxic effects or pathological changes and interferes with various physiological and metabolic processes. Indeed, fluoride reacts with proteins, especially enzymes, and generally inhibits enzyme activity at concentrations in the millimolar range [70, 82]. However, cell proliferation can be stimulated at concentrations in the micromolar range [82,83]. It is not known whether fluoride has any essential function in cells or organisms. Mechanisms by which fluoride affects cell functions include generation of superoxide anion [84,85]; release of cytochrome c from mitochondria and induction of apoptosis [86,87]; inhibition of the migration of embryonic neurons [88] and sperm [85]; and altered release of the neurotransmitters, such as acetylcholine [89] and gammaaminobutyric acid [90].
Excessive fluoride intake or bioaccumulation over a long period of time alters the balance between bone formation and resorption. This biological process is accomplished with the involvement of certain regulatory determinants and signaling pathways, leading to various pathological changes in different bones of skeletal known as “skeletal fluorosis”. In fact, excessive accumulation of fluoride in the bones of the skeleton and associated muscles and ligaments causes different types of deformities which are more dangerous and highly painful depending upon the concentration of fluoride and the duration of its exposure. This entity of longterm intoxication of fluoride is very painful and more dangerous than other forms of fluorosis, e.g. dental fluorosis and is of extreme importance as it reduces mobility at a very early age of the animals by gradually causing different changes in the bones such as periosteal exostosis, osteosclerosis, osteoporosis, and osteophytosis [91-93]. These changes appear clinically as vague aches and pains in the body and joints associated with stiffness, lameness, small body growth, and recognizable bone lesions. These bone changes are progressive and irreversible and become severe with the aging of the animals and increase in duration or frequency of exposure to fluoride. Intermittent lameness, enlarged joints, debility, disability, hoof deformity, wasting of body muscles, and bone lesions in jaw, ribs, metacarpus, and metatarsus regions are well recognized in animals suffering from severe skeletal fluorosis (Figures 1and 2). Ankylosis deformity is also possible in some fluorosis cases. However, this condition is rare in animals suffering from chronic fluoride poisoning. Excessive accumulation of fluoride in muscles also reduces activities or movements and this condition causes lameness in animals.
![Click here to view Large Figure 1](images/JDVS.MS.ID.555942.G001.png)
![Click here to view Large Figure 2](images/JDVS.MS.ID.555942.G002.png)
Fluoride-induced bone lesions include mild to marked periosteal hyperostosis that may be localized or generalized and degenerative joint disease (DJD or arthritis), which can cause severe pain and lameness in domestic animals. Ultimately, these fluoride-induced changes impair general health, fitness, body condition, and may reduce reproductive success or performance. Interestingly, in hoofed animals, the lesions are first observed in the metatarsus or metacarpus bones of the limbs as also found in wild animals [94]. Excessive accumulation of fluoride in muscles also reduces/restricts bone movement leading to lameness in animals. Apart from intermittent lameness, joint swelling, loss of body muscle mass, and mortality are also common in animals with skeletal fluorosis.
Interestingly, all bone changes or lesions are visible only when bone fluoride levels exceed a threshold that is variable across animal species. It appears that the rate of fluoride accumulation in bone influences the type of skeletal lesions observed. Periosteal hyperostosis can develop rapidly if bone fluoride levels are sufficiently high in young individuals and generally develops more slowly in response to chronic exposure and bone fluoride levels increase with increasing age of the animal. However, the severity of bone deformities such as periosteal hyperostosis and osteophytosis increases with increasing bone fluoride levels. In general, fluoride levels in the bones of affected animals are shown to be above “normal” (approximately >1000 μg F/g). A threshold level of approximately 4000 μg F/g dry bone, above which obvious lesions become apparent, has been described in various mammalian species [95-97]. However, according to Underwood (1977) no gross or microscopic changes in bones were found in animals exposed to fluoride levels up to 2,500 ppm [98].
Recent studies show that among various species of domestic animals, bovines (cattle and buffaloes) are found to be relatively less tolerant to fluoride toxicity and suffer from more severe skeletal fluorosis than other animal species. Their calves are also found to be relatively more sensitive to fluoride toxicity than immature animals or juveniles of other species [23,24]. However, apart from fluoride concentration and duration and frequency of exposure and the density and rate of bioaccumulation of fluoride in bones, the prevalence and severity of skeletal fluorosis also depends on many factors, such as age, food, nutrients, chemicals in water, environment, individual sensitivity or tolerance and genetics, etc. [99-109].
Adverse Economic Consequences
It is well known that the rural economy of any country depends largely on animal husbandry. Animal husbandry is also the main source of daily income of the villagers. In villages, people keep and raise animals of different species according to their economic condition and convenience. Animal keepers get sufficient income from milk, dung, meat, leather, bones, wool, etc. obtained from different species of domestic animals. When these animals become victims of skeletal fluorosis, there is a huge reduction in these animal products, which also reduces the income of the animal keepers. Because due to this disease, animals become physically weak and lame, due to which such animals get very low prices when sold in the market, due to which the livestock farmers must suffer huge financial losses. Apart from this, skeletal fluorosis reduces fertility in animals, which ultimately affects animal productivity. If the productivity of animals decreases, then it directly affects the economy of the livestock farmers [110]. Whatever chronic fluoride poisoning in domestic animals is responsible for weakening the rural economy in some way or the other. However, it is difficult to tell how much economic loss animal owners suffer due to skeletal fluorosis in animals. Hence, more scientific studies to assess the economic losses caused by endemic skeletal fluorosis in domestic animals are highly recommended. The findings of these studies may be useful in formulating and implementing health and economic policy to prevent such economic losses.
How To Prevent Skeletal Fluorosis in Domestic Animals
Fluoride-induced skeletal fluorosis is usually permanent, irreversible, and incurable in domestic animals. Therefore, prevention is the only way to protect pets or domestic animals from chronic fluoride toxicosis or skeletal fluorosis. This requires that pets are not fed fluoridated water or exposed to any source of fluoride as far as possible. In areas where almost all drinking groundwater sources are contaminated with fluoride, rainwater harvesting is one of the most ideal and effective methods to get regular fluoride-free water for these animals. Unpolluted water from perennial fresh or surface water sources (ponds, reservoirs, lakes, rivers, etc.) is also an alternative drinking water option for domestic animals as water from these sources contains traces of fluoride or having 0.01–0.3 ppm fluoride [1]. Defluorination of fluoridated water is also an option to provide fluoride-free water to these animals. Though there are many defluorination techniques available. However, “Nalgonda defluorination technique” is an ideal technique for defluorination of fluoride containing water [111]. Nevertheless, providing domestic animals with food rich in natural minerals and antioxidants may be the most effective solution. To protect domestic animals from industrial fluoride emissions or pollution, it is necessary to prevent them from moving to areas where there are factories emitting fluoride. Moving animals from fluoride-affected areas to non-fluorideaffected areas is also an effective way to prevent skeletal fluorosis.
Conclusion
Excessive intake/inhalation of fluoride through fluoridated water and industrial fluoride pollution causes a serious disease called fluorosis in domestic animals. Excessive accumulation of fluoride in various bones of the skeleton causes various deformities or changes in the bones. These deformities caused by fluoride are collectively known as skeletal fluorosis which is extremely painful and persists for life in the animal. Thousands of domesticated animals in fluoride affected areas are found to be suffering from this bone disease. The most dangerous aspect of this disease is that the animals become lame and there is no cure for this disease in animals yet. This disease in animals can also cause financial loss to livestock owners in diverse ways. Therefore, prevention of this disease in domestic animals is extremely important and this is the only solution. This is possible by providing fluoride free drinking water, nutritious food, and shifting animals from fluoride affected areas to non-fluoride affected areas.
Acknowledgement
The author thanks to Prof. Darshana Choubisa, Department Prosthodontics and Crown & Bridge, Geetanjali Dental and Research Institute, Udaipur, Rajasthan 313002, India for cooperation.
References
- Adler P, Armstrong WD, Bell ME, Bhussry BR, Büttner W, et al. (1970) Fluorides and human health. World Health Organization Monograph Series No. 59. Geneva: World Health Organization.
- Choubisa SL, Choubisa DK, Joshi SC, Choubisa L (1997) Fluorosis in some tribal villages of Dungarpur district of Rajasthan, India. Fluoride 30(4): 223-228.
- Swarup D, Dwivedi SK (2002) Environmental pollution and the effect of lead and fluoride on animal health. New Delhi: Indian Council of Agricultural Research.
- Choubisa SL, Choubisa D (2016) Status of industrial fluoride pollution and its diverse adverse health effects in man and domestic animals in India. Environ Sci Poll Res 23(8): 7244-7254.
- Choubisa SL (2018) A brief and critical review of endemic hydrofluorosis in Rajasthan, India. Fluoride 51(1): 13-33.
- Choubisa SL (2018) A brief and critical review on hydrofluorosis in diverse species of domestic animals in India. Environ Geochem Health 40(1): 99-114.
- Choubisa SL (2022) Status of chronic fluoride exposure and its adverse health consequences in the tribal people of the scheduled area of Rajasthan, India. Fluoride 55(1): 8-30.
- Choubisa SL, Choubisa D, Choubisa A (2023) Fluoride contamination of groundwater and its threat to health of villagers and their domestic animals and agriculture crops in rural Rajasthan, India. Environ Geochem Health 45: 607-628.
- Choubisa SL, Pandya H, Choubisa DK, Sharma OP, Bhatt SK, Khan IA (1996) Osteo-dental fluorosis in bovines of tribal region in Dungarpur (Rajasthan). J Environ Biol 17(2): 85-92.
- Choubisa SL (1996) An epidemiological study on endemic fluorosis in tribal areas of southern Rajasthan. A technical report. The Ministry of Environment and Forests, Government of India, New Delhi pp. 1-84.
- Choubisa SL (1999) Chronic fluoride intoxication (fluorosis) in tribes and their domestic animals. Intl J Environ Stud 56(5): 703-716.
- Choubisa SL (1999) Some observations on endemic fluorosis in domestic animals of southern Rajasthan (India). Vet Res Commun 23(7): 457-465.
- Choubisa SL (2000) Fluoride toxicity in domestic animals in Southern Rajasthan. Pashudhan 15(4): 5.
- Choubisa SL (2007) Fluoridated ground water and its toxic effects on domesticated animals residing in rural tribal areas of Rajasthan (India). Intl J Environ Stud 64(2): 151-159.
- Choubisa SL (2008) Dental fluorosis in domestic animals. Curr Sci 95(12):1674-1675.
- Choubisa SL, Mali P (2009) Fluoride toxicity in domestic animals. In: Dadhich L, Sultana F, editors. Proceedings of the National Conference on Environmental Health Hazards, Kota, Rajasthan, India. p.103.
- Choubisa SL (2010) Osteo-dental fluorosis in horses and donkeys of Rajasthan, India. Fluoride 43(1): 5-10.
- Choubisa SL (2010) Fluorosis in dromedary camels of Rajasthan, India. Fluoride 43(3): 194-199.
- Choubisa SL, Mishra GV, Sheikh Z, Bhardwaj B, Mali P, Jaroli VJ (2011) Toxic effects of fluoride in domestic animals. Adv Pharmacol Toxicol 12(2): 29-37.
- Choubisa SL (2012) Status of fluorosis in animals. Proc Natl Acad Sci, India Section B: Biol Sci 82(3): 331-339.
- Choubisa SL (2012) Study of natural fluoride toxicity in domestic animals inhabiting arid and sub-humid ecosystems of Rajasthan. A technical report. University Grants Commission, New Delhi, India pp. 1-29.
- Choubisa SL, Modasiya V, Bahura CK, Sheikh Z (2012) Toxicity of fluoride in cattle of the Indian Thar Desert, Rajasthan, India. Fluoride 45 (4): 371-376.
- Choubisa SL (2013) Fluorotoxicosis in diverse species of domestic animals inhabiting areas with high fluoride in drinking waters of Rajasthan, India. Proc Natl Acad Sci, India Section B: Biol Sci 83(3): 317-321.
- Choubisa SL (2013) Fluoride toxicosis in immature herbivorous domestic animals living in low fluoride water endemic areas of Rajasthan, India: an observational survey. Fluoride 46(1): 19-24.
- Choubisa SL (2013) A note on bovine calves as ideal bio-indicators for endemic fluorosis. Indian Water Works Association; Proceedings of IWWA-National Seminar- 2013, Water- Present & Future, Jodhpur, Rajasthan, India, pp. 169-171.
- Choubisa SL, Mishra GV (2013) Fluoride toxicosis in bovines and flocks of desert environment. Intl J Pharmacol Biol Sci 7(3): 35-40.
- Choubisa SL (2014) Bovine calves as ideal bio-indicators for fluoridated drinking water and endemic osteo-dental fluorosis. Environ Monit Assess 186 (7): 4493-4498.
- Choubisa SL (2015) Industrial fluorosis in domestic goats (Capra hircus), Rajasthan, India. Fluoride 48(2): 105-115.
- Choubisa SL (2021) Chronic fluoride exposure and its diverse adverse health effects in bovine calves in India: an epitomised review. Global J Biol Agric Health Sci 10(3): 1-6. Or 10:107.
- Choubisa SL, Choubisa A (2021) A brief review of ideal bio-indicators, biomarkers, and determinants of endemic of fluoride and fluorosis. J Biomed Res Environ Sci 2(10): 920-925.
- Choubisa SL (2022) A brief and critical review of chronic fluoride poisoning (fluorosis) in domesticated water buffaloes (Bubalus bubalis) in India: focus on its impact on rural economy. J Biomed Res Environ Sci 3(1): 96-104.
- Choubisa SL (2022) A brief review of chronic fluoride toxicosis in the small ruminants, sheep, and goats in India: focus on its adverse economic consequences. Fluoride 55(4): 296-310.
- Choubisa SL (2023) Endemic hydrofluorosis in cattle (Bos taurus) in India: an epitomised review. Intl J Vet Sci Technol 8(1): 001-007.
- Choubisa SL (2023) Industrial fluoride emissions are dangerous to animal health, but most ranchers are unaware of it. Austin Med Sci 8(1): 1-4.
- Choubisa SL (2023) A brief review of industrial fluorosis in domesticated bovines in India: focus on its socio-economic impacts on livestock farmers. J Biomed Res 4(1): 8-15.
- Choubisa SL (2023) Chronic fluoride poisoning in domestic equines, horses (Equus caballus) and donkeys (Equus asinus). J Biomed Res 4(1): 29-32.
- Choubisa SL (2023) A brief review of endemic fluorosis in dromedary camels (Camelus dromedarius) and focus on their fluoride susceptibility. Austin J Vet Sci Anim Husband 10(1): 1-6.
- Choubisa SL (2023) Is drinking groundwater in India safe for domestic animals with respect to fluoride? Archives Anim Husband Dairy Sci 2(4): 1-7.
- Choubisa SL (2023) Is it safe for domesticated animals to drink fresh water in the context of fluoride poisoning? Clinic Res Anim Sci 3(2): 1-5.
- Choubisa SL (2024) Are bovine calves ideal bio-indicators for endemic fluorosis? J Vet Sci Res 9(1): 1-8.
- Shupe JL, Olson AE, Sharma RP (1979) Effects of fluoride in domestic and wild animals. Hazard Toxic Subst. 2.
- Shupe JL, Olson AE (1982) Clinical and pathological aspects of fluoride toxicosis in animals. In 'Fluorides: effects on vegetation, animals and humans.’ Paragon Press: Utah State University, Logan, Utah, USA.
- Suttie JW, Hamilton RJ, Clay AC, Tobin ML, Moore WG (1985) Effects of fluoride ingestion on white-tailed deer (Odocoileus virginianus). J Wildl Dis 21(3): 283-288.
- Van Paemel M, Dierick N, Janssens G, Fievez V, De Smet S (2010) Selected trace and ultratrace elements: Biological role, content in feed and requirements in animal nutrition – Elements for risk assessment. EFSA Supporting Publications 7(7): 68E.
- Kierdorf U, Death C, Hufschmid J, Witzel C, Kierdorf H (2016) Developmental and post-eruptive defects in molar enamel of free-ranging eastern grey kangaroos (Macropus giganteus) exposed to high environmental levels of fluoride. PLoS One 11(2): e0147427.
- Shupe JL, Olson AE, Peterson HB, Low JB (1984) Fluoride toxicosis in wild ungulates. J Am Vet Med Assoc 185(11): 1295-1300.
- Kierdorf U, Kierdorf H, Sedlacek F, Fejerskov O (1996) Structural changes in fluorosed dental enamel of red deer (Cervus elaphus L.) from a region with severe environmental pollution by fluorides. J Anat 188(1): 183-195.
- Choubisa SL (2024) Can fluoride exposure be dangerous to the health of wildlife? If so, how can they be protected from it? J Vet Med Anim Sci 7(1): 1-6.
- Choubisa SL, Sompura K, Bhatt SK, Choubisa DK, Pandya H, Joshi SC, Choubisa L (1996) Prevalence of fluorosis in some villages of Dungarpur district of Rajasthan. Indian J Environ Health 38(2): 119-126.
- Choubisa SL, Verma R (1996) Skeletal fluorosis in bone injury case. J Environ Biol 17(1): 17-20.
- Choubisa SL, Sompura K (1996) Dental fluorosis in tribal villages of Dungarpur district (Rajasthan). Poll Res 15(1): 45-47.
- Choubisa SL (1998) Fluorosis in some tribal villages of Udaipur district (Rajasthan). J Environ Biol 19(4): 341-352.
- Sompura K, Choubisa SL (1999) Some observations on endemic fluorosis in the villages of Sagawara Panchayat Samiti of Dungarpur district, Rajasthan. In: Proceedings of National Seminar on Fluoride, Fluorosis and Defluoridation Techniques, MLS University, Udaipur, India, pp 66-69.
- Choubisa SL (2001) Endemic fluorosis in southern Rajasthan (India). Fluoride 34(1): 61-70.
- Choubisa SL, Choubisa L, Choubisa DK (2001) Endemic fluorosis in Rajasthan. Indian J Environ Health 43(4): 177-189.
- Choubisa SL (2012) Fluoride in drinking water and its toxicosis in tribals, Rajasthan, India. Proc Natl Acad Sci, India Section B: Biol Sci 82(2): 325-330.
- Choubisa SL, Choubisa D (2015) Neighbourhood fluorosis in people residing in the vicinity of superphosphate fertilizer plants near Udaipur city of Rajasthan (India). Environ Monit Assess 187(8): 497.
- Choubisa SL, Choubisa D (2019) Genu-valgum (knock-knee) syndrome in fluorosis- endemic Rajasthan and its status in India. Fluoride 52(2): 161-168.
- Choubisa SL (2023) Is drinking groundwater in India safe for human health in terms of fluoride? J Biomed Res 4(1): 64-71.
- Choubisa SL, Choubisa D, Choubisa A (2023) Can people get fluorosis from drinking water from surface water sources? Fluoride test of water mandatory before its supply. SciBase Epidemiol Publ Health 1(2): 1006.
- Choubisa SL (2024) Focus on dangerous skeletal fluorosis, how it can be prevented in humans. Poll on Commun Health Effects. Manuscript ID Number: PCHE-EL-2024-021.
- Choubisa SL, Sompura K, Choubisa DK, Pandya H, Bhatt SK, Sharma OP, Parmar L (1995) Fluoride content in domestic water sources of Dungarpur district of Rajasthan. Indian J Environ Health 37(3): 154-160.
- Choubisa SL, Sompura K, Choubisa DK, Sharma OP (1996) Fluoride in drinking water sources of Udaipur district of Rajasthan. Indian J Environ Health 38(4): 286-291.
- Choubisa SL (1997) Fluoride distribution and fluorosis in some villages of Banswara district of Rajasthan. Indian J Environ Health 39(4): 281-288.
- Choubisa SL (2018) Fluoride distribution in drinking groundwater in Rajasthan, India. Curr Sci 114(9): 1851-1857.
- Choubisa SL (2022) The diagnosis and prevention of fluorosis in humans. J Biomed Res Environ Sci 3(3): 264-267.
- Choubisa SL (2022) How can fluorosis in animals be diagnosed and prevented? Austin J Vet Sci Anim Husband 9(3): 1-5.
- Choubisa SL (2023) Is industrial fluoride pollution harmful to agricultural crops? Farmers need to know. Environ Analys Ecol Stud 000761.11(3): 1261-1266.
- Choubisa SL (2023) Is naturally fluoride contaminated groundwater irrigation safe for the health of agricultural crops in India? Poll Commun Health Effects 1(2):1-8.
- Barbier O, Arreola-Mendoza L, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188(2): 319-333.
- EFSA (2005) Opinion of the scientific panel on dietetic products, nutrition, and allergies on a request from the Commission related to the tolerable upper intake level of fluoride (Request No EFSAQ-2003-018). EFSA J 192: 1-65.
- Whitford GM, Sampaio FC, Pinto CS, Maria AG, Cardoso VE, Buzalaf MA (2008) Pharmacokinetics of ingested fluoride: lack of effect of chemical compound. Arch Oral Biol 53(11): 1037-1041.
- Gutknecht J, Walter A (1981) Hydrofluoric and nitric acid transport through lipid bilayer membranes. Biochim Biophys Acta 644(1): 153-156.
- Caldera R, Chavinie J, Fermanian J, Tortrat D, Laurent AM (1988) Maternal-fetal transfer of fluoride in pregnant women. Biol Neonate 54(5): 263-269.
- Shen YW, Taves DR (1974) Fluoride concentrations in the human placenta and maternal and cord blood. American J Obstet Gynecol 119(2): 205-207.
- ATSDR (2003) Agency for toxic substances and disease registry; toxicological profile for fluorides, hydrogen fluoride, and fluorine. US Department of Health and Human Services. Public Health Service, Atlanta, GA.
- Ekstrand J, Alvan G, Boreus LO, Norlin A (1977) Pharmacokinetics of fuoride in man after single and multiple oral doses. European J Clin Pharmacol 12(4):311-317.
- Taves DR, Forbes N, Silverman D, Hicks D (1983) Inorganic fluoride concentrations in human and animal tissues. Fluorides: Effects on Vegetation, Animals and Humans Ed Shupe J, Peterson, H, Leone, N Paragon Press, Salt Lake City, Utah, USA: 189-193.
- Villa A, Anabalon M, Zohouri V, Maguire A, Franco AM, Rugg-Gunn A (2010) Relationships between fluoride intake, urinary fluoride excretion and fluoride retention in children and adults: an analysis of available data. Caries Res 44(1): 60-68.
- Weinstein LH and Davison AW (2004) Fluoride in the environment. CABI Publishing: Oxon, UK. 2004.
- Whitford GM (1996) The metabolism and toxicity of fluoride.' monographs in oral science, Karger: Basel.
- Mendoza-Schulz A, Solano-Agama C, Arreola-Mendoza L, Reyes-Márquez B, Barbier O, et al. (2009) The effects of fluoride on cell migration, cell proliferation, and cell metabolism in GH4C1 pituitary tumor cells. Toxicol Lett 190(2): 179-186.
- Adamek E, Pawlowska-Goral K, Bober K (2005) In vitro and in vivo effects of fluoride ions on enzyme activity. Ann Acad Med Stetin 51(2): 69-85.
- Garcia-Montalvo EA, Reyes-Perez H, Del Razo LM (2009) Fluoride exposure impairs glucose tolerance via decreased insulin expression and oxidative stress. Toxicology 263(2-3): 75-83.
- Izquierdo-Vega JA, Sanchez-Gutierrez M, Del Razo LM (2008) Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss. Toxicol Appl Pharmacol 230(3): 352-357.
- Chlubek D, Grucka-Mamczar E, Birkner E, Polaniak R, Stawiarska Piȩta B, Duliban H (2003) Activity of pancreatic antioxidative enzymes and malondialdehyde concentrations in rats with hyperglycemia caused by fluoride intoxication. J Trace Elem Med Bio 17(1): 57-60.
- Lee JH, Jung JY, Jeong YJ, Park JH, Yang KH, et al. (2008) Involvement of both mitochondrial-and death receptor-dependent apoptotic pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the human gingival fibroblasts. Toxicology 243(3): 340-347.
- Horgan AM, Lagrange MT, Copenhaver PF (1994) Developmental expression of G proteins in a migratory population of embryonic neurons. Development 120(4): 729-742.
- Flora SJ, Mittal M, Mishra D (2009) Co-exposure to arsenic and fluoride on oxidative stress, glutathione linked enzymes, biogenic amines, and DNA damage in mouse brain. J Neurol Sci 285(1-2): 198-205.
- Gardiner IM, de Belleroche J (1990) Modulation of gamma-aminobutyric acid release in cerebral cortex by fluoride, phorbol ester, and phosphodiesterase inhibitors: differential sensitivity of acetylcholine release to fluoride and K+ channel blockers. J Neurochem 54(4): 1130-1135.
- Choubisa SL (1996) Radiological skeletal changes due to chronic fluoride intoxication in Udaipur district (Rajasthan). Poll Res 15(3): 227-229.
- Choubisa SL (2012) Toxic effects of fluoride on bones. Adv Pharmacol Toxicol 13(1): 9-13.
- Choubisa SL (2022) Radiological findings are more important and reliable in the diagnosis of skeletal fluorosis. Austin Med Sci 7(2):1-4, id1069.
- Shupe JL, Miner ML, Greenwood DA, Butcher JE, Nielsen HM (1963) The effect of fluorine on dairy cattle II. Clinical and pathologic effects. American J Vet Res 24: 964-979.
- Death C, Coulson G, Kierdorf U, Kierdorf H, Morris WK, Hufschmid J (2015) Dental fluorosis and skeletal fluoride content as biomarkers of excess fluoride exposure in marsupials. Sci Total Environ 533: 528-541.
- Shupe JL (1980) Clinicopathologic features of fluoride toxicosis in cattle. J Anim Sci 51(3): 746-758.
- Turner CH, Boivin G, Meunier PJ (1993) A mathematical model for fluoride uptake by the skeleton. Calcified Tissue Intl 52(2): 130-138.
- Underwood EJ (1977) Trace elements in human and animal nutrition. 4th Edition, Academic Press, New York.
- Choubisa SL, Choubisa L, Sompura K, Choubisa D (2007) Fluorosis in subjects belonging to different ethnic groups of Rajasthan. J Commun Dis 39(3): 171-177.
- Choubisa SL, Choubisa L, Choubisa D (2009) Osteo-dental fluorosis in relation to nutritional status, living habits and occupation in rural areas of Rajasthan, India. Fluoride 42(3): 210-215.
- Choubisa SL, Choubisa L, Choubisa D (2010) Osteo-dental fluorosis in relation to age and sex in tribal districts of Rajasthan, India. J Environ Sci Engg 52(3): 199-204.
- Choubisa SL (2010) Natural amelioration of fluoride toxicity (fluorosis) in goats and sheep. Curr Sci 99(10): 1331-1332.
- Choubisa SL, Choubisa L, Choubisa D (2011) Reversibility of natural dental fluorosis. Intl J Pharmacol Biol Sci 5(20): 89-93.
- Choubisa SL, Mishra GV, Sheikh Z, Bhardwaj B, Mali P, Jaroli VJ (2011) Food, fluoride, and fluorosis in domestic ruminants in the Dungarpur district of Rajasthan, India. Fluoride 44(2): 70-76.
- Choubisa SL (2012) Osteo-dental fluorosis in relation to chemical constituents of drinking waters. J Environ Sci Engg 54(1): 153-158.
- Choubisa SL (2013) Why desert camels are least afflicted with osteo-dental fluorosis? Curr Sci 105(12): 1671-1672.
- Choubisa SL, Choubisa D, Choubisa P (2023) Are tribal people in India relatively more susceptible to fluorosis? More research is needed on this. Poll Commun Health Effects 1(2):1-10.
- Choubisa SL (2024) Are sheep and goat animals relatively more tolerant to fluorosis? J Vet Med Res 11(1): 1-5.
- Choubisa SL (2024) Is the water buffalo species (Bubalus bubalis) relatively more sensitive to fluorosis than other species of domestic animals? Still, there is a need for more in-depth research on this. J Vet Med Anim Sci 7(1): 1-6.
- Choubisa SL (2023) A brief and critical review of endemic fluorosis in domestic animals of scheduled area of Rajasthan, India: focus on its impact on tribal economy. Clinic Res Anim Sci 3(1):1-11.
- Choubisa SL (2023) Nalgonda technique is an ideal technique for defluoridation of water: its use can prevent and control hydrofluorosis in humans in India. Acad J Hydrol Water Resourc 1(1): 15-21.