Early-life Co-exposure to fluoride and lead modifies the tissue distribution of essential and toxic trace elements

Exposure to toxic metals such as lead (Pb) during early development is known to induce long-lasting physiological and neurological effects. However, little is known about how co-exposure to fluoride (F)-a common environmental and dietary element-modulates Pb toxicokinetics and the homeostasis of other trace elements in soft and mineralized tissues. This study aimed to evaluate the effects of early-life exposure to Pb (30 µg/L) and/or F (50 µg/L) on the distribution of nine trace elements (Al, As, Ba, Cd, Cu, Mn, Pb, Sr, and Zn) in soft organs (brain, heart, kidney, liver) and bone of Wistar rats. Animals were exposed via drinking water from gestation until postnatal day 30. Elemental concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), and group differences were considered statistically significant at p < 0.0013 (Bonferroni-corrected). Co-exposure to Pb and F resulted in a 2-fold increase in Pb concentrations in the brain and a 40-fold increase in the kidney. Fluoride exposure alone increased Mn in the liver, while Pb exposure alone led to elevated levels of Al, As, Ba, and Pb in the heart; As in the brain and kidney; Mn and Zn in the liver; and Cu in the kidney. Notably, co-exposure modified the distribution of several elements beyond Pb, including reductions in Cd and As in soft tissues and altered deposition of bone-seeking elements like Sr and Ba. To our knowledge, this is the first study demonstrating that fluoride can alter lead distribution and significantly affect the soft-tissue metallomic profile during early development. These findings highlight the importance of considering metal-metal interactions in environmental toxicology and suggest that fluoride may act as a modifier of metal toxicity. Further studies are warranted to investigate the functional consequences of these alterations and their implications for organ development and health outcomes in exposed populations.