A bayesian benchmark dose–based assessment of the neuro-safety reference of urinary fluoride: implications for revising current Chinese standards

• A 1 mg/L increase in urinary fluoride was associated with a 5% higher risk of cognitive impairment in adults from a fluorosis area. • A neurotoxicity-based safety reference value for urinary fluoride (BMDL = 1.18 mg/L) was derived using a Bayesian Benchmark Dose Modeling (BBMD) system. • The derived reference is lower than China’s current standard, urging a dual-reference-value system to protect both neurological and skeletal health. High fluoride exposure has been linked to neurological impairment; however, evidence on the safety threshold for fluoride-induced neurotoxicity remains limited. A cross-sectional study was undertaken in a fluorosis-affected area with drinking water in Jishan County, Shanxi Province. Urinary fluoride was used as the biomarker of fluoride exposure and measured using an ion-selective electrode method. Cognitive function was assessed with the Mini-Mental State Examination (MMSE). Multivariable linear regression and binary logistic regression were employed to examine the dose–response relationship between urinary fluoride and cognitive performance. The Bayesian Benchmark Dose (BBMD) system was used to estimate the safety reference for urinary fluoride. Higher urinary fluoride levels were significantly associated with cognitive impairment. Upon controlling for possible confounders, each 1 mg/L increment in urine fluoride correlated with a 5% elevated risk of cognitive impairment (OR = 1.05, 95% CI: 1.01–1.09). At a benchmark response (BMR) of 5%, the benchmark dose (BMD) was 3.12 mg/L, with a 95% lower bound (BMDL) of 1.18 mg/L. Elevated urinary fluoride is an independent associated factor for cognitive dysfunction. The neuroprotective safety reference value of 1.0 mg/L for urinary fluoride estimated in this study is lower than the current Chinese reference standard, indicating that more rigorous regulations may be necessary to safeguard the nervous system from excessive fluoride exposure. These findings offer novel scientific information to guide measures for reducing fluoride-induced neurotoxicity.