Spatiotemporal distribution, health risk assessment, and preventable disease burden of dental and skeletal fluorosis via defluoridation scenarios in Fars Province, Iran.

Abstract

Original abstract online at
https://link.springer.com/article/10.1007/s10653-026-03474-4

Fluoride contamination in groundwater poses a persistent public health challenge in arid regions, where elevated concentrations lead to dental and skeletal fluorosis. Current defluoridation policy evaluations have overlooked the population health benefits of interventions, the variability in technology performance, and the direct link between treatment efficacy and health outcomes. Hence, this study employed a comprehensive spatiotemporal probabilistic health risk assessment with disease burden estimation. It integrated disability-adjusted life years (DALY)-based intervention policy modeling and kernel density estimation to create a strategic framework. In this method, intervention scenarios were stochastically modeled using literature-derived fluoride-removal efficiency ranges. Groundwater samples (n = 7,722) were collected from counties of Fars Province, Iran, during 2015–2020. Hierarchical clustering delineated four fluoride risk zones: low (LFZ), moderate (MFZ), high (HFZ), and extreme (XFZ). The highest proportions of exceedance rates of hazard quotient (%HQ > 1) were concentrated in southern and southwestern zones across all age groups. Dental fluorosis was the dominant health outcome, with XFZ encompassing a cumulative burden of 669.14 (95% UI: 478.54–859.74) DALYs and normalized rates up to 1888.55 (1461.59–2315.52) per 100,000. Skeletal fluorosis contributed to lower burdens in all clusters, yet the burden was as high as 132.95 (115.23–150.67), with a rate of 458.72 (442.42–475.01) per 100,000 in XFZ. The probabilistic evaluation of nine defluoridation policies revealed reverse osmosis and ion exchange/precipitation as the most effective interventions, achieving >98% and 96% reductions in DALYs, respectively. These methods significantly outperformed alternatives like phytoremediation (60–90% reduction) and nutritional interventions (<50% reduction). For all policies, the percentage reduction in DALYs was the same for dental and skeletal outcomes. The proposed framework in this research supports prioritization of defluoridation interventions and demonstrates how probabilistic health-risk modeling can inform adaptive water governance and resource allocation in fluorosis-endemic regions.

Data availability
No datasets were generated or analysed during the current study.

Supplementary Information
Supplementary file1 (DOCX 3282 kb) (download DOCX )

References

Abera, A., Aseffa, A., Mengistie, B., Malmqvist, E., Isaxon, C., & Sahilu, G. (2025). Probabilistic human health risk assessment from groundwater fluoride contamination in Main Ethiopia Rift. Scientific Reports, 15(1), 28571. https://doi.org/10.1038/s41598-025-13821-7

Article CAS Google Scholar
Abtahi, M., Dobaradaran, S., Jorfi, S., Koolivand, A., Khaloo, S. S., Spitz, J., Saeedi, H., Golchinpour, N., & Saeedi, R. (2019). Age-sex specific disability-adjusted life years (DALYs) attributable to elevated levels of fluoride in drinking water: A national and subnational study in Iran, 2017. Water Research, 157, 94–105. https://doi.org/10.1016/j.watres.2019.03.087

Article CAS Google Scholar
Ahmad, S., Singh, R., Arfin, T., & Neeti, K. (2022). Fluoride contamination, consequences and removal techniques in water: A review. Environmental Science: Advances, 1(5), 620–661. https://doi.org/10.1039/D1VA00039J

Article CAS Google Scholar
Akakuru, O. C., Akaolisa, C. C. Z., Aigbadon, G. O., Eyankware, M. O., Opara, A. I., Obasi, P. N., Ofoh, I. J., Njoku, A. O., & Akudinobi, B. E. B. (2023a). Integrating machine learning and multi-linear regression modeling approaches in groundwater quality assessment around Obosi, SE Nigeria. Environment, Development and Sustainability, 25(12), 14567–14606. https://doi.org/10.1007/s10668-022-02679-8

Article Google Scholar
Akakuru, O. C., Eyankware, M. O., Akakuru, O. U., Nkwoada, A. U., & Agunanne, V. C. (2023b). Quantification of contamination, ecological risk index, and health risk assessment of groundwater using artificial neural network and multi-linear regression modeling approaches within Egbema, Nigeria. Arabian Journal of Geosciences, 16(9), 507. https://doi.org/10.1007/s12517-023-11600-0

Article Google Scholar
Akakuru, O. C., Eze, C. U., Okeke, O. C., Opara, A. I., Usman, A. O., Iheme, O., Ibeneme, S. I., & Iwuoha, P. O. (2022). Hydrogeochemical evolution, water quality indices, irrigation suitability and pollution index of groundwater (PIG) around eastern Niger Delta, Nigeria. International Journal of Energy and Water Resources, 6(3), 389–411. https://doi.org/10.1007/s42108-021-00162-0

Article Google Scholar
Ali, S., Ali, H., Pakdel, M., Ghale Askari, S., Mohammadi, A. A., & Rezania, S. (2022). Spatial analysis and probabilistic risk assessment of exposure to fluoride in drinking water using GIS and Monte Carlo simulation. Environmental Science and Pollution Research, 29(4), 5881–5890. https://doi.org/10.1007/s11356-021-16075-8

Article CAS Google Scholar
Aliaskari, M., & Schäfer, A. I. (2021). Nitrate, arsenic and fluoride removal by electrodialysis from brackish groundwater. Water Research, 190, 116683. https://doi.org/10.1016/j.watres.2020.116683

Article CAS Google Scholar
Amadi, C. C., Okeke, C. O., Onyekuru, S. O., Okereke, C. N., & Akakuru, O. C. (2025). Assessing groundwater pollution using advanced statistical techniques and pollution indices near a coal fly ash dump in parts of Oji-river, Nigeria. Environmental Science and Pollution Research, 32(29), 17801–17823. https://doi.org/10.1007/s11356-025-36672-1

Article CAS Google Scholar
APHA. (2018). Standard methods for the examination of water and wastewater. American Public Health Association. https://doi.org/10.2105/SMWW.2882.081

Book Google Scholar
Asgari, G., Dayari, A., Ghasemi, M., Seid-mohammadi, A., Gupta, V. K., & Agarwal, S. (2019). Efficient fluoride removal by preparation, characterization of pyrolysis bone: Mixed level design experiment and Taguchi L8 orthogonal array optimization. Journal of Molecular Liquids, 275, 251–264. https://doi.org/10.1016/j.molliq.2018.10.137

Article CAS Google Scholar
Asgari, G., salari, M., Seidmohammadi, A., Akbari-adergani, B., Mahvi, A. H., Kamari, N., Rastegar, K. E., & Faraji, H. (2025). Investigation and risk assessment of fluoride concentration in drinking water, soil and food products in Hamedan rural areas. Scientific Reports, 15(1), 18458. https://doi.org/10.1038/s41598-025-99462-2

Article CAS Google Scholar
Cao, W., Zhang, Z., Guo, H., Fu, Y., Gao, Z., Nan, T., Ren, Y., & Li, Z. (2023). Spatial distribution and controlling mechanisms of high fluoride groundwater in the coastal plain of Bohai Rim, North China. Journal of Hydrology, 617, 128952. https://doi.org/10.1016/j.jhydrol.2022.128952

Article CAS Google Scholar
Chowdhury, A., Adak, M. K., Mukherjee, A., Dhak, P., Khatun, J., & Dhak, D. (2019). A critical review on geochemical and geological aspects of fluoride belts, fluorosis and natural materials and other sources for alternatives to fluoride exposure. Journal of Hydrology, 574, 333–359. https://doi.org/10.1016/j.jhydrol.2019.04.033

Article CAS Google Scholar
D’Alessandro, W., Bellomo, S., & Parello, F. (2012). Fluorine adsorption by volcanic soils at Mt. Etna, Italy. Applied Geochemistry, 27(6), 1179–1188. https://doi.org/10.1016/j.apgeochem.2012.02.028

Article CAS Google Scholar
Das, K., Puppala, H., Pandey, G., Mondal, M., Pathak, P., Dey, U., Chell, S., Dutta, S., & Kumar, P. (2025). Community level vulnerability of groundwater fluoride contamination and exposure by the application of multi-criteria model. Journal of Hazardous Materials Advances, 17, 100555. https://doi.org/10.1016/j.hazadv.2024.100555

Article CAS Google Scholar
Derakhshani, E., Miri, M. R., Arab-Zozani, M., Gholamzadeh, M., & Naghizadeh, A. (2025). Sustainable household water treatment systems based on reverse osmosis (RO) in ensuring safe drinking water: A systematic review of assessing physicochemical water quality changes and future outlook. Physics and Chemistry of the Earth, Parts a/b/c, 141, 104131. https://doi.org/10.1016/j.pce.2025.104131

Article Google Scholar
Dey Bhowmik, A., Das, T., & Chattopadhyay, A. (2023). Chronic exposure to environmentally relevant concentration of fluoride impairs osteoblast’s collagen synthesis and matrix mineralization: Involvement of epigenetic regulation in skeletal fluorosis. Environmental Research, 236, 116845. https://doi.org/10.1016/j.envres.2023.116845

Article CAS Google Scholar
Duvva, L. K., Panga, K. K., Dhakate, R., & Himabindu, V. (2021). Health risk assessment of nitrate and fluoride toxicity in groundwater contamination in the semi-arid area of Medchal, South India. Applied Water Science, 12(1), Article 11. https://doi.org/10.1007/s13201-021-01557-4

Article CAS Google Scholar
Edmunds, W. M., & Smedley, P. L. (2013). Essentials of medical geology (Vol. 13, pp. 311–336)

Book Google Scholar
Elisadiki, J., Jande, Y. A. C., Kibona, T. E., & Machunda, R. L. (2020). Highly porous biomass-based capacitive deionization electrodes for water defluoridation. Ionics, 26(5), 2477–2492. https://doi.org/10.1007/s11581-019-03372-z

Article CAS Google Scholar
Eminagaoglu, M., Oskay, R. G., & Karayigit, A. I. (2022). Evaluation of elemental affinities in coal using agglomerative hierarchical clustering algorithm: A case study in a thick and mineable coal seam (kM2) from Soma Basin (W. Turkey). International Journal of Coal Geology, 259, 104045. https://doi.org/10.1016/j.coal.2022.104045

Article CAS Google Scholar
Enalou, H. B., Moore, F., Keshavarzi, B., & Zarei, M. (2018). Source apportionment and health risk assessment of fluoride in water resources, south of Fars province, Iran: Stable isotopes (?18O and ?D) and geochemical modeling approaches. Applied Geochemistry, 98, 197–205. https://doi.org/10.1016/j.apgeochem.2018.09.019

Article CAS Google Scholar
Farías, P., Estevez-García, J. A., Onofre-Pardo, E. N., Pérez-Humara, M. L., Rojas-Lima, E., Álamo-Hernández, U., & Rocha-Amador, D. O. (2021). Fluoride exposure through different drinking water sources in a contaminated basin in Guanajuato, Mexico: A deterministic human health risk assessment. International Journal of Environmental Research and Public Health. https://doi.org/10.3390/ijerph182111490

Article Google Scholar
Fars Meteorological Bureau. (2022). https://www.farsmet.ir/Default.aspx
Fewtrell, L., Smith, S., Kay, D., & Bartram, J. (2006). An attempt to estimate the global burden of disease due to fluoride in drinking water. Journal of Water and Health, 4(4), 533–542. https://doi.org/10.2166/wh.2006.0036

Article CAS Google Scholar
Ganyaglo, S. Y., Gibrilla, A., Teye, E. M., Owusu-Ansah, E.D.-G.J., Tettey, S., Diabene, P. Y., & Asimah, S. (2019). Groundwater fluoride contamination and probabilistic health risk assessment in fluoride endemic areas of the Upper East Region, Ghana. Chemosphere, 233, 862–872. https://doi.org/10.1016/j.chemosphere.2019.05.276

Article CAS Google Scholar
Gao, T., Wang, X. C., Chen, R., Ngo, H. H., & Guo, W. (2015). Disability adjusted life year (DALY): A useful tool for quantitative assessment of environmental pollution. Science of the Total Environment, 511, 268–287. https://doi.org/10.1016/j.scitotenv.2014.11.048

Article CAS Google Scholar
Gbadebo, A. M., Ofili, E., Duru, C. M., Makanjuola, O. O., Gbadebo, O. O., Igwe, D. O., Osianor, E. O., Otubu, K. A., Adegbanke, G. T., Owoola, I. M., Bello, A. A., Egbedara, T. A., Ola-Iya, I. E., Adesanya, A. D., Omolafe, O. F., Samuel, C. E., Francis, V. J., Michael, T. K., & Dimowo, B. O. (2026). Health risk assessment of nitrate and fluoride in groundwater across 10 Nigerian states. Environmental Geochemistry and Health, 48(5), 221. https://doi.org/10.1007/s10653-026-03064-4

Article CAS Google Scholar
Ghaemi, Z., & Noshadi, M. (2022). Surface water quality analysis using multivariate statistical techniques: A case study of Fars Province rivers, Iran. Environmental Monitoring and Assessment, 194(3), 178. https://doi.org/10.1007/s10661-022-09811-1

Article CAS Google Scholar
Ghaemi, Z., & Noshadi, M. (2024). Evaluation of fluoride exposure using disability-adjusted life years and health risk assessment in south-western Iran: A novel Monte Carlo simulation. Ecotoxicology and Environmental Safety, 282, 116705. https://doi.org/10.1016/j.ecoenv.2024.116705

Article CAS Google Scholar
Ghanbari, E., Ghaemi, Z., Rajabi, S., Mohammadi Ashnani, M. H., Giesy, J. P., Shin, H.-M., & Mohammadpour, A. (2026). Comparative assessment of risks due to exposure to fluoride in tap and reverse osmosis water. Physics and Chemistry of the Earth, Parts a/b/c, 144, 104466. https://doi.org/10.1016/j.pce.2026.104466

Article Google Scholar
Ghanbarian, M., Ghanbarian, M., Tabatabaie, T., Ghanbarian, M., & Ghadiri, S.-K. (2022). Distributing and assessing fluoride health risk in urban drinking water resources in Fars Province, Iran, using the geographical information system. Environmental Geochemistry and Health, 44(3), 771–781. https://doi.org/10.1007/s10653-021-00982-3

Article CAS Google Scholar
Gispert, M. Í., Hernández, M. A., Climent, E. L., & Flores, M. F. (2018). Rainwater harvesting as a drinking water option for Mexico City. Sustainability. https://doi.org/10.3390/su10113890

Article Google Scholar
Iamandii, I., De Pasquale, L., Giannone, M. E., Veneri, F., Generali, L., Consolo, U., Birnbaum, L. S., Castenmiller, J., Halldorsson, T. I., Filippini, T., & Vinceti, M. (2024). Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis. Environmental Research, 242, 117759. https://doi.org/10.1016/j.envres.2023.117759

Article CAS Google Scholar
Iwar, R. T., Ogedengbe, K., Katibi, K. K., & Jabbo, J. N. (2021). Fluoride levels in deep aquifers of Makurdi, North-central, Nigeria: An appraisal based on multivariate statistics and human health risk analysis. Environmental Monitoring and Assessment, 193(8), Article 477.

Article CAS Google Scholar
Karunanidhi, D., Rajan, M., Roy, P. D., & Subramani, T. (2025). Seasonal effects on groundwater fluoride and evaluating health hazards: In-situ remediation via managed aquifer recharge. Geoscience Frontiers, 16(5), 102102. https://doi.org/10.1016/j.gsf.2025.102102

Article CAS Google Scholar
Kashyap, S. J., Sankannavar, R., & Madhu, G. M. (2021). Fluoride sources, toxicity and fluorosis management techniques: A brief review. Journal of Hazardous Materials Letters, 2, 100033. https://doi.org/10.1016/j.hazl.2021.100033

Article CAS Google Scholar
Kaur, L., Rishi, M. S., & Siddiqui, A. U. (2020). Deterministic and probabilistic health risk assessment techniques to evaluate non-carcinogenic human health risk (NHHR) due to fluoride and nitrate in groundwater of Panipat, Haryana, India. Environmental Pollution, 259, 113711. https://doi.org/10.1016/j.envpol.2019.113711

Article CAS Google Scholar
Kheradpisheh, Z., Mirzaei, M., Mahvi, A. H., Mokhtari, M., Azizi, R., Fallahzadeh, H., & Ehrampoush, M. H. (2018). Impact of drinking water fluoride on human thyroid hormones: A case-control study. Scientific Reports, 8(1), 2674. https://doi.org/10.1038/s41598-018-20696-4

Article CAS Google Scholar
Kim, D., Cánovas-Segura, B., Campos, M., & Juarez, J. M. (2024). Visualization of spatial–temporal epidemiological data: A scoping review. Technologies. https://doi.org/10.3390/technologies12030031

Article Google Scholar
Krisher, L., Butler-Dawson, J., Yoder, H., Pilloni, D., Dally, M., Johnson, E. C., Jaramillo, D., Cruz, A., Asensio, C., & Newman, L. S. (2020). Electrolyte beverage intake to promote hydration and maintain kidney function in Guatemalan sugarcane workers laboring in hot conditions. Journal of Occupational and Environmental Medicine, 62(12), e696–e703. https://doi.org/10.1097/JOM.0000000000002033

Article Google Scholar
Kumar, M., Das, A., Das, N., Goswami, R., & Singh, U. K. (2016). Co-occurrence perspective of arsenic and fluoride in the groundwater of Diphu, Assam, Northeastern India. Chemosphere, 150, 227–238. https://doi.org/10.1016/j.chemosphere.2016.02.019

Article CAS Google Scholar
Kumar, R., Sharma, P., Yang, W., Sillanpää, M., Shang, J., Bhattacharya, P., Vithanage, M., & Maity, J. P. (2022). State-of-the-art of research progress on adsorptive removal of fluoride-contaminated water using biochar-based materials: Practical feasibility through reusability and column transport studies. Environmental Research, 214, 114043. https://doi.org/10.1016/j.envres.2022.114043

Article CAS Google Scholar
Li, L., Ma, L., Pan, Z., Xu, J., Chen, F., Yang, C., & Yin, Y. (2025). Spatial distribution and health risk assessment of fluoride in groundwater in the oasis of the Hotan river basin in Xinjiang, China. Scientific Reports, 15(1), 11630. https://doi.org/10.1038/s41598-025-96583-6

Article CAS Google Scholar
Li, Y., Zhang, M., Mi, W., Ji, L., He, Q., Xie, S., Xiao, C., & Bi, Y. (2024). Spatial distribution of groundwater fluoride and arsenic and its related disease in typical drinking endemic regions. Science of the Total Environment, 906, 167716. https://doi.org/10.1016/j.scitotenv.2023.167716

Article CAS Google Scholar
Liu, J., Yang, S., Luo, M., Chen, T., Ma, X., Tao, N., Zhao, X., & Wang, D. (2020). Association between dietary patterns and fluorosis in Guizhou, China. Frontiers in Nutrition, 6, 189. https://doi.org/10.3389/fnut.2019.00189

Article CAS Google Scholar
Long, H., Zeng, J., Wei, S., Hu, T., Lu, Y., Jia, Q., Li, J., Ye, H., Gao, Y., Zhang, Z., & Luo, P. (2026). Predicting skeletal fluorosis severity using machine learning across diverse fluoride-exposed populations in China. Scientific Reports, 16(1), 13858. https://doi.org/10.1038/s41598-026-43429-4

Article CAS Google Scholar
Mianeh, H. Y., Amiri, L., Jafari, A., & Nourozi, N. (2025). Health risk assessment via Monte Carlo simulation and sensitivity analysis for fluoride and nitrate content in bottled waters consumed in Kermanshah city, Iran. Scientific Reports, 15(1), 5008. https://doi.org/10.1038/s41598-025-89439-6

Article CAS Google Scholar
Mizelle, E., Larson, K. L., Bolin, L. P., & Kearney, G. D. (2022). Fluid intake and hydration status among North Carolina farmworkers: A mixed methods study. Workplace Health and Safety, 70(12), 532–541. https://doi.org/10.1177/21650799221117273

Article Google Scholar
Mohammadi, A. A., Yousefi, M., Yaseri, M., Jalilzadeh, M., & Mahvi, A. H. (2017). Skeletal fluorosis in relation to drinking water in rural areas of West Azerbaijan, Iran. Scientific Reports, 7(1), 17300. https://doi.org/10.1038/s41598-017-17328-8

Article CAS Google Scholar
Mukherjee, I., & Singh, U. K. (2022). Exploring a variance decomposition approach integrated with the Monte Carlo method to evaluate groundwater fluoride exposure on the residents of a typical fluorosis endemic semi-arid tract of India. Environmental Research, 203, 111697. https://doi.org/10.1016/j.envres.2021.111697

Article CAS Google Scholar
Mukherjee, I., Singh, U. K., & Patra, P. K. (2019). Exploring a multi-exposure-pathway approach to assess human health risk associated with groundwater fluoride exposure in the semi-arid region of east India. Chemosphere, 233, 164–173. https://doi.org/10.1016/j.chemosphere.2019.05.278

Article CAS Google Scholar
Müllner, D. (2011). Modern hierarchical, agglomerative clustering algorithms (arXiv:1109.2378; Version 1). arXiv. https://doi.org/10.48550/arXiv.1109.2378
Mulualem, D., Hailu, D., Tessema, M., & Whiting, S. J. (2022). Association of dietary calcium intake with dental, skeletal and non-skeletal fluorosis among women in the Ethiopian Rift Valley. International Journal of Environmental Research and Public Health. https://doi.org/10.3390/ijerph19042119

Article Google Scholar
Mwiathi, N. F., Gao, X., Li, C., & Rashid, A. (2022). The occurrence of geogenic fluoride in shallow aquifers of Kenya Rift Valley and its implications in groundwater management. Ecotoxicology and Environmental Safety, 229, 113046. https://doi.org/10.1016/j.ecoenv.2021.113046

Article CAS Google Scholar
Narsimha, A., & Sudarshan, V. (2017). Contamination of fluoride in groundwater and its effect on human health: A case study in hard rock aquifers of Siddipet, Telangana State, India. Applied Water Science, 7(5), 2501–2512. https://doi.org/10.1007/s13201-016-0441-0

Article CAS Google Scholar
Nasrollahi, Y., Khoshravesh, M., & Aghajani Mazandarani, G. (2025). New improvement ion exchange treatment method for drinking water in Juybar City, Iran. Applied Water Science, 15(7), 182. https://doi.org/10.1007/s13201-025-02551-w

Article CAS Google Scholar
Oghenenyoreme Eyankware, M., Akakuru, O. C., Igwe, E. O., Olajuwon, W. O., & Ukor, K. P. (2024). Pollution indices, potential ecological risks and spatial distribution of heavy metals in soils around Delta State, Nigeria. Water, Air, and Soil Pollution, 235(7), 452. https://doi.org/10.1007/s11270-024-07209-y

Article CAS Google Scholar
Ousman, W. Z., Alemayehu, E., & Luis, P. (2025). Fluoride removal and recovery from groundwater using an integrated reverse osmosis–membrane crystallization process. Clean Technologies. https://doi.org/10.3390/cleantechnol7020040

Article Google Scholar
Patel, P. P., Patel, P. A., Zulf, M. M., Yagnik, B., Kajale, N., Mandlik, R., Khadilkar, V., Chiplonkar, S. A., Phanse, S., Patwardhan, V., Joshi, P., Patel, A., & Khadilkar, A. V. (2017). Association of dental and skeletal fluorosis with calcium intake and serum vitamin D concentration in adolescents from a region endemic for fluorosis. Indian Journal of Endocrinology and Metabolism, 21(1), 190–195. https://doi.org/10.4103/2230-8210.196013

Article CAS Google Scholar
Pérez-Galicia, A., Torrico-Lavayen, R., Jiménez-Cordova, M. I., Martínez-Alvarado, M. D. R., Ayllon-Vergara, J. C., Arreola-Mendoza, L., Barrera-Hernández, A., Sanchez-Guerra, M., Del Razo, L. M., & Osorio-Yáñez, C. (2025). Left ventricular mass and systolic function in children environmentally exposed to fluoride. Environmental Research, 281, 121932. https://doi.org/10.1016/j.envres.2025.121932

Article CAS Google Scholar
Qiu, Y., Ren, L.-F., Shao, J., Xia, L., & Zhao, Y. (2022). An integrated separation technology for high fluoride-containing wastewater treatment: Fluoride removal, membrane fouling behavior and control. Journal of Cleaner Production, 349, 131225. https://doi.org/10.1016/j.jclepro.2022.131225

Article CAS Google Scholar
Rahman, M. M., Bodrud-Doza, M., Siddiqua, M. T., Zahid, A., & Islam, A. R. M. T. (2020). Spatiotemporal distribution of fluoride in drinking water and associated probabilistic human health risk appraisal in the coastal region, Bangladesh. Science of the Total Environment, 724, 138316. https://doi.org/10.1016/j.scitotenv.2020.138316

Article CAS Google Scholar
Rajan, S., & Nandimandalam, J. R. (2024). Environmental health risk assessment and source apportion of heavy metals using chemometrics and pollution indices in the upper Yamuna river basin, India. Chemosphere, 346, 140570. https://doi.org/10.1016/j.chemosphere.2023.140570

Article CAS Google Scholar
Rosner, B., Glynn, R. J., & Lee, M.-L.T. (2006). The Wilcoxon signed rank test for paired comparisons of clustered data. Biometrics, 62(1), 185–192.

Article Google Scholar
Sawangjang, B., Hashimoto, T., Wongrueng, A., Wattanachira, S., & Takizawa, S. (2019). Assessment of fluoride intake from groundwater and intake reduction from delivering bottled water in Chiang Mai province, Thailand. Heliyon, 5(9), e02391. https://doi.org/10.1016/j.heliyon.2019.e02391

Article CAS Google Scholar
Saylor, C., Malin, A. J., Tamayo-Ortiz, M., Cantoral, A., Amarasiriwardena, C., Estrada-Gutierrez, G., Tolentino, M. C., Pantic, I., Wright, R. O., Tellez-Rojo, M. M., & Sanders, A. P. (2022). Early childhood fluoride exposure and preadolescent kidney function. Environmental Research, 204, 112014. https://doi.org/10.1016/j.envres.2021.112014

Article CAS Google Scholar
Sharma, G. K., Meena, G. L., Ali, S., Jena, R. K., Kumar, K., Kumar, A., Rashmi, I., Nogiya, M., Kumawat, A., Mohanty, R. K., Das, B., Gupta, A., & Madhu, M. (2026). Hydrogeochemical modelling and the probabilistic health risk assessment of nitrate and fluoride in the groundwater of Kota stone mine regions. Environmental Science: Water Research and Technology, 12(3), 1003–1020. https://doi.org/10.1039/D5EW00905G

Article CAS Google Scholar
Shen, J., & Schäfer, A. (2014). Removal of fluoride and uranium by nanofiltration and reverse osmosis: A review. Chemosphere, 117, 679–691. https://doi.org/10.1016/j.chemosphere.2014.09.090

Article CAS Google Scholar
Singh Solanki, Y., Agarwal, M., Gupta, S., Shukla, P., Maheshwari, K., & Midda, M. O. (2019). Application of synthesized Fe/Al/Ca based adsorbent for defluoridation of drinking water and its significant parameters optimization using response surface methodology. Journal of Environmental Chemical Engineering, 7(6), 103465. https://doi.org/10.1016/j.jece.2019.103465

Article CAS Google Scholar
Smith, F. A., Hodge, H. C., & Dinman, B. D. (1977). Airborne fluorides and man: Part I. CRC Critical Reviews in Environmental Control, 8(1–4), 293–371. https://doi.org/10.1080/10643387709381665

Article Google Scholar
Srivastava, S., & Flora, S. J. S. (2020). Fluoride in drinking water and skeletal fluorosis: A review of the global impact. Current Environmental Health Reports, 7(2), 140–146. https://doi.org/10.1007/s40572-020-00270-9

Article CAS Google Scholar
Statistical Center of Iran. (2017). General population and housing census 2016. https://www.amar.org.ir
Su, H., Kang, W., Kang, N., Liu, J., & Li, Z. (2021). Hydrogeochemistry and health hazards of fluoride-enriched groundwater in the Tarim Basin, China. Environmental Research, 200, 111476. https://doi.org/10.1016/j.envres.2021.111476

Article CAS Google Scholar
Su, H., Li, H., Chen, H., Li, Z., & Zhang, S. (2023). Source identification and potential health risks of fluoride and nitrate in groundwater of a typical alluvial plain. Science of the Total Environment, 904, 166920. https://doi.org/10.1016/j.scitotenv.2023.166920

Article CAS Google Scholar
Taghipour, N., Amini, H., Mosaferi, M., Yunesian, M., Pourakbar, M., & Taghipour, H. (2016). National and sub-national drinking water fluoride concentrations and prevalence of fluorosis and of decayed, missed, and filled teeth in Iran from 1990 to 2015: A systematic review. Environmental Science and Pollution Research, 23(6), 5077–5098. https://doi.org/10.1007/s11356-016-6160-0

Article CAS Google Scholar
Timm, C., Luther, S., Jurzik, L., Hamza, I. A., & Kistemann, T. (2016). Applying QMRA and DALY to assess health risks from river bathing. Safe Ruhr, 219(7, Part B), 681–692. https://doi.org/10.1016/j.ijheh.2016.07.017

Article Google Scholar
Ultsch, A., & Lötsch, J. (2022). Euclidean distance-optimized data transformation for cluster analysis in biomedical data (EDOtrans). BMC Bioinformatics, 23(1), 233. https://doi.org/10.1186/s12859-022-04769-w

Article CAS Google Scholar
USEPA. (1992). USEPA guidelines for exposure assessment. Risk Assessment Forum.

Google Scholar
USEPA. (2025). https://www.epa.gov/waterresilience/online-water-quality-monitoring-resources
Veneri, F., Iamandii, I., Vinceti, M., Birnbaum, L. S., Generali, L., Consolo, U., & Filippini, T. (2023). Fluoride exposure and skeletal fluorosis: A systematic review and dose-response meta-analysis. Current Environmental Health Reports, 10(4), 417–441. https://doi.org/10.1007/s40572-023-00412-9

Article CAS Google Scholar
Verma, D. R., & Yadav, N. (2024). Advances in low-cost defluoridation techniques for safe drinking water with respect to innovations and plant-based adsorbents (Vol. 20).
Wang, F., Li, Y., Tang, D., Zhao, J., Yang, X., Liu, Y., Peng, F., Shu, L., Wang, J., He, Z., & Liu, Y. (2021). Effects of water improvement and defluoridation on fluorosis-endemic areas in China: A meta-analysis. Environmental Pollution, 270, 116227. https://doi.org/10.1016/j.envpol.2020.116227

Article CAS Google Scholar
Wang, M., Li, X., He, W., Li, J., Zhu, Y., Liao, Y.-L., Yang, J., & Yang, X. (2019). Distribution, health risk assessment, and anthropogenic sources of fluoride in farmland soils in phosphate industrial area, southwest China. Environmental Pollution, 249, 423–433. https://doi.org/10.1016/j.envpol.2019.03.044

Article CAS Google Scholar
Wei, J., Yang, Q., Xie, X., Yang, J., Wu, B., Si, C., & Yang, F. (2024). A novel hybrid approach for revealing the genesis and spatiotemporal variation of high fluoride groundwater under natural and anthropogenic influences. Journal of Hydrology, 641, 131782. https://doi.org/10.1016/j.jhydrol.2024.131782

Article CAS Google Scholar
Wei, Z., Li, X., Yuan, C., Tang, K., Liu, L., Long, X., & Wang, C. (2026). Controlling mechanisms and health risk assessment of high fluoride geothermal water in the Pearl River Delta region, South China. Journal of Hazardous Materials, 513, 142474. https://doi.org/10.1016/j.jhazmat.2026.142474

Article CAS Google Scholar
WHO. (2011). World Health Organization (WHO) Guidelines for drinking water quality (3rd ed).
WHO. (2024). Global strategy and action plan on oral health 2023–2030. World Health Organization.

Google Scholar
Wilcoxon, F. (1945). Individual comparisons by ranking methods. Biometrics Bulletin, 1(6), 80–83. https://doi.org/10.2307/3001968

Article Google Scholar
Witten, I. H., & Frank, E. (2002). Data mining: Practical machine learning tools and techniques with Java implementations. ACM SIGMOD Record, 31(1), 76–77.

Article Google Scholar
Xu, N., Peng, M., Li, Q., & Xu, C. (2020). Towards consistent interpretations of coal geochemistry data on whole-coal versus ash bases through machine learning. Minerals, 10(4), 328.

Article CAS Google Scholar
Zhang, L., Huang, D., Yang, J., Wei, X., Qin, J., Ou, S., Zhang, Z., & Zou, Y. (2017). Probabilistic risk assessment of Chinese residents’ exposure to fluoride in improved drinking water in endemic fluorosis areas. Environmental Pollution, 222, 118–125. https://doi.org/10.1016/j.envpol.2016.12.074

Article CAS Google Scholar
Zhang, R., Luo, M., Wu, L., Yan, S., Li, A., Mo, Z., Zafar, G., Wu, D., Li, X., Gao, N., Wang, X., & Pei, J. (2026). Association between relatively low fluoride exposure and bone mineral density in children and adolescents: Insights from NHANES and a wistar rat model of fluorosis. Ecotoxicology and Environmental Safety, 311, 119828. https://doi.org/10.1016/j.ecoenv.2026.119828

Article CAS Google Scholar
Zhang, Y., Gao, Y., & Liu, X. (2024). Focus on cognitive impairment induced by excessive fluoride: An update review. Neuroscience, 558, 22–29. https://doi.org/10.1016/j.neuroscience.2024.08.011

Article CAS Google Scholar
Zheng, D., Liu, Y., Luo, L., Shahid, M. Z., & Hou, D. (2020). Spatial variation and health risk assessment of fluoride in drinking water in the Chongqing urban areas, China. Environmental Geochemistry and Health, 42(9), 2925–2941. https://doi.org/10.1007/s10653-020-00532-3

Article CAS Google Scholar

Download references

Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Authors and Affiliations

Department of Water Engineering, Shiraz University, Shiraz, Iran

Zeynab Ghaemi, Masoud Noshadi & Rezvan Talebnejad

Contributions
Zeynab Ghaemi: conceptualization, methodology, software, validation, formal analysis, investigation, data curation, writing—original draft, resources, visualization, writing—review and editing. Masoud Noshadi and Rezvan Talebnejad: supervision, review and editing.

Corresponding author
Correspondence to Masoud Noshadi.

Ethics declarations
Conflict of interest
The authors declare no competing financial or personal interests.

Research Studies

Study Tracker

Spatiotemporal distribution, health risk assessment, and preventable disease burden of dental and skeletal fluorosis via defluoridation scenarios in Fars Province, Iran.

Abstract